Details of a Researcher - Kurihara, Toshihide

Papers - Kurihara, Toshihide

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Effect of Anti-VEGF Therapy on Wide-Field Retinal and Choroidal Thickness in Macular Edema Secondary to Retinal Vein Occlusion

Araki R, Tomita Y†, Yuda T, Jiang X, Ban N, Kunimi H, Uchida A, Kurihara T, Shinoda H, Negishi K

AJO Int. (Elsevier BV) 100207 2025.12

Accepted, ISSN 2950-2535

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Polarized Light Microscopy-Based Quantification of Scleral Collagen Fiber Bundle Remodeling in the Lens-Induced Myopia Mouse Model

Yang Y*, Ikeda SI*, Kang L, Ma Z, Negishi K, Tsubota K, Tomita Y, Gettinger K, Kurihara T†

Life. 15 ( 11 ) 1743 2025.11

Last author, Corresponding author, Accepted

Scleral remodeling plays a crucial role in myopia development. Although ultrastructural collagen changes have been described, quantitative assessment at the fiber bundle level remains limited. This study quantitatively evaluated scleral collagen remodeling in a lens-induced myopia (LIM) mouse model using polarized light microscopy (PLM) combined with picrosirius red (PSR) staining. LIM was induced in C57BL/6J male mice by applying a monocular −30 D lens from postnatal week 3 to 6. Eyes wearing −30 D lenses showed myopic shifts in refraction (−8.42 ± 3.87 D vs. 4.42 ± 4.45 D; p = 0.002) and axial elongation (0.21 ± 0.04 mm vs. 0.18 ± 0.05 mm; p = 0.020) compared with contralateral controls. PLM revealed looser, more disorganized collagen bundles in myopic sclera. Quantitative analysis showed reduced bundle proportion (40.91 ± 6.58% vs. 48.36 ± 6.47%; p = 0.040) and mean size (147.11 ± 59.38 µm2 vs. 281.45 ± 101.00 µm2; p = 0.002). These results indicate that myopia development involves structural remodeling of the sclera and that PLM with PSR staining provides a practical approach for quantitative wide-field evaluation of collagen architecture in experimental myopia.

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Choroidal Mast Cells and Their Degranulation Are a Pivotal Trigger for Myopia Development.

Shi J*, Ikeda SI*, Fukuchi*., Chen J, Gettinger K, Imanishi S, Negishi K, Tsubota K, Kurihara T†

Invest Ophthalmol Vis Sci. 66 ( 14 ) 22 2025.11

Last author, Corresponding author, Accepted, ISSN 01460404

PURPOSE: Mast cells (MCs), key immune regulators, contribute to inflammatory responses through their degranulation. Choroidal thinning is a hallmark of myopia, and MC degranulation has been shown to induce choroidal thinning in a rat model of geographical atrophy. However, the role of choroidal MCs in myopia remains poorly understood. This study aimed to demonstrate that an increased number and proportion of degranulated MCs in the choroid are important determinants of choroidal thinning and myopia development. METHODS: Lens-induced myopia (LIM) was induced by monocular -30 diopter (D) lens wearing in C57BL/6 mice, MC-deficient mice (Mcpt5/Cma1DTR/+), and MC-deficient mice receiving suprachoroidal injection of peritoneal MCs (PMCs). Cromolyn sodium (cromolyn) and pemirolast potassium (pemirolast), reagents that inhibit degranulation by stabilizing MC membranes, were topically applied in LIM mice. Ocular parameters including refraction, axial length, and choroidal thickness were measured before and after LIM. Choroidal MC degranulation was evaluated by choroidal flatmount staining. RESULTS: LIM was successfully induced in wild-type mice but was significantly suppressed in MC-deficient mice. Suprachoroidal injection of PMCs into MC-deficient mice restored myopia progression, as evidenced by axial elongation and choroidal thinning. MC degranulation was significantly increased by -30 D lens wearing, whereas topical administration of cromolyn and pemirolast effectively inhibited both MC degranulation and myopia progression. CONCLUSIONS: Choroidal MC degranulation plays a critical role in LIM by promoting choroidal thinning and axial elongation. These findings enhance our understanding of the role of choroidal MC degranulation in myopia, suggesting a potential therapeutic target for myopia treatment.

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Validation of phiC31-mediated expression and functional knockout of Opn3 in the Opn3-phiC31o knock-in mouse

Kwok RKY, Ikuta H*, Iba C*, Nakano Y*, Ma Z*, Chuai Y, Hiraoka Y, Sayanagi T, Kurihara T, Moritoh S†, Tanaka KF

Eye Vis. (Springer Science and Business Media LLC) 12 ( 1 ) 41 2025.10

Accepted

Abstract

Background

Opn3 is a non-visual blue light-sensitive opsin that has recently been reported to have an expansive repertoire of biological functions. To investigate the function of Opn3-expressing cells, we aimed to generate a system in which Opn3-expressing cells can be targeted by site-specific gene recombination.

Methods

Opn3-phiC31o knock-in (KI) mice were generated using the CRISPR-Cas9 method. The phiC31o-poly(A) cassette was inserted into the translation start site in exon 1. Opn3 mRNA and phiC31o mRNA were visualized by in situ hybridization (ISH). 5' rapid amplification of cDNA end (5' RACE) analysis was performed using RNAs from wild-type mouse cerebral cortex and cerebellum to identify the transcription start site of Chml, predicted to be shared with the transcription start site of Opn3. Cold-induced decrease in body temperature was monitored with a telemetric probe to confirm the phenotype of Opn3 knockout. To examine the phiC31o integrase-mediated recombination, Opn3-phiC31o mice were crossed with the ROSA26 MultiFPsΔPuro reporter and cyan fluorescent protein, mCerulean, expression was labeled by immunohistochemistry.

Results

The expression pattern of phiC31o mRNA was consistent with that of Opn3 mRNA in Opn3-phiC31o heterozygous mouse brains, indicating that phiC31o mRNA is expressed under the control of the Opn3 promoter. Based on the public database, the transcription start site of exon 1 of Opn3 is identical to that of Chml, suggesting that phiC31o KI disrupts Chml expression. However, Opn3-phiC31o homozygous mice sustained Chml expression, and the transcription start site of Chml was confirmed to be located 112 bp upstream of the predicted second exon. Opn3-phiC31o homozygous mice showed a larger decrease in body temperature under cold exposure compared to wild-type controls. In addition, these mice also exhibited a refractive myopia phenotype. These findings confirmed the functional knockout of Opn3. Double transgenic mice of Opn3-phiC31o and ROSA26 MultiFPsΔPuro reporter showed mCerulean expression mainly in the olfactory bulb, cerebral cortex, thalamus, and cerebellum. The recombination efficiency was 30% to 44% in the cerebellum.

Conclusions

Opn3-phiC31o KI mice were successfully generated. We can generate Opn3 null mice that does not disrupt Chml by preparing homozygotes of Opn3-phiC31o. We have deposited the sequences including the newly found transcription start site of Chml.

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Diabetic Retinopathy, a Comprehensive Overview on Pathophysiology and Relevant Experimental Models

Gettinger K, Lee D, Tomita Y, Negishi K, Kurihara T†

Int J Mol Sci. (MDPI AG) 26 ( 20 ) 9882 - 9882 2025.10

Last author, Corresponding author, Accepted, ISSN 16616596

Diabetic retinopathy (DR) is a serious complication of diabetes, leading to vision loss worldwide. The prevalence of DR has increased in recent decades. To understand the pathophysiology of DR, various experimental models have been developed and used. In this review article, we first outline what is currently known of the general pathology of DR, including the mechanisms involved in hyperglycemia, vascular dysfunction, retinal ischemia, retinal inflammation, and retinal degeneration. We next summarize various pathologies detected in experimental models in vivo, such as in chemically and genetically induced murine, rat, and monkey models, surgical methods in larger animals like cats, and a novel murine DR model using occlusion of the carotid artery under early diabetic conditions. A general overview of the in vitro models, including cell monocultures, co-cultures, and 3D models, is also provided. This current summary enables further research to obtain a more thorough understanding of DR pathogenesis and develop appropriate treatment measures.

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An analysis of light that reaches the eye surface in an outdoor environment

Jiang X*, Kondo S*, Otsuka N, Kaneda D, Torii H, Negishi K, Kurihara T†, Tsubota K†

Sci Rep. (Springer Science and Business Media LLC) 15 ( 1 ) 34319 2025.10

Corresponding author, Accepted

The global pandemic of myopia has become an urgent public health concern in recent years. Although the mechanism remains largely unclear, the importance of outdoor light exposure on myopia prevention is widely recognized. Outdoor light is more intense and has a different spectral composition compared to indoor lighting, which are believed to contribute to the suppression of myopia. However, due to modern lifestyles, even children find it difficult to spend time outdoors. To receive outdoor light efficiently is important, yet previous reports showed inconsistent findings on optimal thresholds for outdoor light exposure. One reason may be the lack of a standardized protocol for measuring light reaching the eye surface. In this study, we developed a novel measurement device using a 3D-printed mannequin head with a light sensor probe embedded at the eye position to mimic the human eye. We assessed the proportion of light that reached the mannequin’s eye surface from different directions at various time points on a sunny day and evaluated the influence of different eyeglasses and lenses.

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Flanged intrascleral intraocular lens fixation using 31 needles

Nagamoto T, Kurihara T, Negishi K, Ban N†

Retin Cases Brief Rep. (Ovid Technologies (Wolters Kluwer Health)) 2025.10

Accepted, ISSN 1935-1089

Purpose:

To demonstrate the novel use of a 31-gauge needle for flanged intrascleral intraocular lens (IOL) fixation using the double-needle technique.

Methods:

Flanged intrascleral IOL fixation was performed using the ZELOSTAT 31G (ASTI, Shizuoka, Japan) needle in a 73-year-old male with right IOL subluxation.

Results:

The IOL was successfully fixated with smooth intraoperative handling, excellent postoperative outcomes, no complications, and minimal refractive error.

Conclusion:

The 31-gauge needle has a larger inner diameter compared to the conventional 30-gauge thin-wall needle, which may facilitate intrascleral IOL fixation procedures.

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Impact of Extended Lens-Induced Myopia on Retinal Structure and Function in Mice

Yang Y*, Tomita Y*, Lee D, Ikeda SI, Jiang X, Negishi K, Tsubota K†, Kurihara T†

Curr Eye Res. doi.org/10.1080/02713683.2025.2557590 2025.09

Last author, Corresponding author, Accepted, ISSN 02713683

Purpose: To investigate time-dependent structural and functional retinal alterations in a mouse model of prolonged lens-induced myopia. Methods: Myopia was induced in male C57BL/6J mice by fitting −30 D lenses on both eyes starting at postnatal week 3. Mice were assigned to either a long-term induction group (3–9 weeks of age) or a short-term induction group (3–6 weeks of age). Separate groups fitted with 0 D lenses served as controls. Ocular parameters, including refraction, axial length, choroidal thickness, and retinal thickness were measured at weeks 3, 6, and 9 using an infrared photorefractor and spectral-domain optical coherence tomography. Retinal function was assessed by dark-adapted electroretinography at week 9 for the long-term group and at week 6 for the short-term group. Statistical analyses included two-way repeated-measures ANOVA followed by Bonferroni’s post hoc test for comparisons across groups and time points, and two-tailed unpaired t-test or one-way ANOVA with Fisher’s LSD post hoc test for group comparisons at individual time points. Results: After 6 weeks of myopia induction, the long-term myopia group exhibited significant reduction in refraction, axial length elongation, and choroidal thickness thinning. Inner retinal thickness was markedly reduced, and electroretinography revealed attenuated amplitudes and delayed implicit times of the oscillatory potentials. Conclusion: Prolonged lens-induced myopia in mice induces time-dependent structural and functional retinal alterations, particularly in the inner layers. This model underscores the significance of early retinal monitoring under long-term myopic conditions and serves as a platform for investigating retinal vulnerability and developing preservation strategies over time.

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Digital health as a scalable strategy for equitable myopia management in East Asia

Chen J*, Lee D*, Negishi K, Tsubota K, Kurihara T†

Asia Pac J Ophthalmol. (Elsevier BV) 14 ( 6 ) 100241 2025.08

Last author, Corresponding author, Accepted, ISSN 2162-0989

East Asia is facing a growing burden of myopia, with pronounced disparities in access to eye care between urban and rural populations. Digital health technologies present a scalable and cost-effective alternative to traditional myopia interventions that enhance early detection, risk stratification, behavioral modification, and public education. Artificial intelligence-assisted screening tools, wearable monitors, and mHealth initiatives, such as the World Health Organization-International Telecommunication Union MyopiaEd program, have demonstrated effectiveness in improving myopia prevention and health education accessibility. However, achieving a sustained impact requires rigorous validation, robust data governance, infrastructure investment, and integration with established clinical strategies. East Asia could be well-positioned to pioneer a comprehensive digital model for equitable myopia control.

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Mechanisms Underlying Myopia Progression from Visual Signaling to Metabolic Remodeling in Retina

Yang Y, Lee D, Gettinger K, Tsubota K, Negishi K, Kurihara T, Tomita Y†

JMA J. (Japan Medical Association) 8 ( 4 ) DOI: 10.31662/jmaj.2025-0268 2025.08

Accepted, ISSN 2433-328X

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Dose-dependent myopia-suppressing effect of 4-phenlybutyric acid eye drops in a mouse myopia model under masked condition

Ikeda SI, Sone K, Takai Y, Miyano T, Negishi K, Tsubota K, Kurihara T†

BMC Ophthalmol 25 ( 1 ) 383 2025.07

Last author, Corresponding author, Accepted

Background: Myopia, characterized by excessive axial elongation of the eyeball, has become a significant global public health issue, particularly in Asia. Severe myopia increases the risk of ocular complications, including retinal degeneration and glaucoma. Recent studies have identified the role of scleral extracellular matrix remodeling and endoplasmic reticulum (ER) stress in myopia pathogenesis. Our previous study identified scleral ER stress as a critical factor in myopia development. This study aimed to investigate the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone, in mitigating scleral ER stress and its effects on myopia progression in a mouse myopia model under masked condition. Methods: A lens-induced myopia (LIM) mouse model was utilized to evaluate the effects of 4-PBA administered as eye drops. Mice received varying concentrations of 4-PBA or phosphate-buffered saline (PBS) as a control. Changes in refractive error and axial length were measured to assess myopia progression. In addition, further experiments were also conducted under masked conditions, where the experimenter was unaware of the treatment was being applied, for the three conditions of 2%, 0.5% 4-PBA eye drops or vehicle treatment of LIM mice. Results: Administration of 4-PBA at concentrations of 0.5% and higher significantly suppressed the myopic shift in refraction and axial elongation associated with myopia compared to mice in the PBS control group. In a blinded, masked experiment, 2% and 0.5% 4-PBA eye drops also suppressed the progression of myopia in a dose-dependent manner. Conclusions: This study demonstrated that 4-PBA effectively mitigated myopia progression in a mouse model by targeting scleral ER stress. The dose-dependent suppression of myopic shifts and axial elongation under masked experimental condtion highlights the potential of 4-PBA as a therapeutic agent for managing myopia. These findings pave the way for further research and potential clinical applications in myopia treatment.

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Antibiotics-Induced Gut Microbiome Dysbiosis Affects Susceptibility to Minus Lens-Induced Myopia in Mice

Ikeda SI, Lee D, Chen J, Fukuda S, Negishi K, Tsubota K†, Kurihara T†

Invest Ophthal Vis Sci. (Association for Research in Vision and Ophthalmology (ARVO)) 66 ( 6 ) 76 2025.06

Last author, Corresponding author, Accepted, ISSN 1552-5783

PURPOSE. The prevalence of myopia has increased worldwide in recent decades, shifting the focus in research from genetic to environmental factors. The roles of diet in the development of myopia may be directly associated with gut microbiota composition. Therefore this study evaluated the effects of antibiotic-induced gut dysbiosis on the development of negative lens-induced myopia. METHODS. We administered several antibiotics (ampicillin, vancomycin, neomycin, or a mixture) to induce gut dysbiosis in male C57BL/6J mice with negative lens-induced myopia. Gut microbiome profiles were analyzed by 16 S rRNA gene sequencing. RESULTS. Mice administered vancomycin, neomycin, and a mixture of three antibiotics exhibited resistance to lens-induced myopia, unlike control or ampicillin-administered mice. Further analyses revealed no specific trend in the gut microbiota composition and diversity related to myopia resistance, except for an increase in the abundance of Clostridiaceae. CONCLUSIONS. These findings demonstrate the potential role of the gut microbiome, particularly Clostridiaceae family, in myopia susceptibility. This study offers new insights into the preventive strategies and therapeutic interventions to mitigate myopia development.

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Evaluation of Anti-VEGFR2 Specific Photoimmunotherapy for Targeted Regression of Neovascularization in an AMD Model

Osada H, Nishimura T, Mitsunaga M, Saruta M, Tsubota K, Negishi K, Kurihara T, Ban N†

Invest Ophthalmol Vis Sci. (Association for Research in Vision and Ophthalmology (ARVO)) 66 ( 6 ) 70 2025.06

Accepted, ISSN 1552-5783

PURPOSE. This study aimed to evaluate the efficacy of photoimmunotherapy (PIT) targeting VEGFR2 for the treatment of neovascular AMD and to investigate its potential as a novel therapeutic strategy. METHODS. DC101-IR700, a conjugate of the anti-mouse VEGFR2 monoclonal antibody DC101 and the photosensitizer IR700, was investigated both in vitro and in vivo. VEGFR2 expression in endothelial cells was confirmed via qPCR and immunocytochemistry. Laser-induced choroidal neovascularization (CNV) was established in C57BL/6J mice. Localization of DC101-IR700 within CNV lesions was assessed by immunofluorescence. After PIT was performed using either a 690 nm near-infrared manual laser or a slit lamp laser, CNV volumes were quantified through confocal microscopy. Cell viability post PIT was measured using MTT assay and cell death in CNV lesions was evaluated using TUNEL staining. RESULTS. DC101-IR700 localized specifically to VEGFR2-positive cells in CNV lesions, and PIT induced significant VEGFR2-dependent cytotoxicity in vitro. In vivo, both PIT and directional PIT using slit lamp laser significantly reduced CNV volumes compared with controls. TUNEL staining confirmed VEGFR2-specific cell death in treated CNV lesions. Directional PIT achieved similar efficacy to PIT, demonstrating its potential as a clinically viable alternative. CONCLUSIONS. PIT targeting VEGFR2 selectively induced cell death in pathological neovascular tissues, significantly reducing CNV volume in an AMD model. These findings suggest that VEGFR2-specific PIT represents a promising and targeted approach for treating neovascular AMD, offering advantages over conventional anti-VEGF therapies by potentially decreasing treatment frequency and improving efficacy.

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Thicker peripapillary choroid may be associated with behavioral factors in Tokyo's children.

Hashimoto A*, Yotsukura E*, Ogawa M, Mori K, Hanyuda A, Tsubota K, Kurihara T, Negishi K†, Torii H†

Sci Rep. 15 ( 1 ) 17868 - 17868 2025.05

Accepted

The study goals were measurement of the choroidal thickness (CT) and investigation of related factors among children. Third-grade students at an elementary school in Tokyo participated in this study. A total of 119 schoolchildren underwent measurements of the axial length (AL), non-cycloplegic objective refraction (SE), and CT. The CT was divided into nine regions: the subfoveal area with a diameter of 1 mm (C0), a 5-mm-diameter circle-C0 (C1), and a 9-mm-diameter circle (C2); each was further divided into four quadrants. The SE, AL, and C0 CT were, respectively, - 1.57 ± 1.56 diopters, 23.39 ± 0.80 mm, and 297.73 ± 57.88 μm. Multiple regression analysis showed that the time spent using a computer was associated significantly with the CT in the C0 and the inferior C2 (C0: β = -0.728, P = 0.028; inferior C2: β = -0.527, P = 0.048), and the reading distance was associated significantly with the CT in the superior and nasal C2 (superior, β = 1.664, P = 0.007; nasal, β = 1.128, P = 0.015). In addition, time spent using smartphones, tablets, or handheld gaming devices was associated significantly with the CT in the superior and inferior C2 (superior C2: β = 0.259, P = 0.018; inferior C2: β = 0.262, P = 0.013). In conclusion, reading distance and time spent on digital devices may be associated with choroid thickness in children.

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Intensive outdoor activity for 1 week increases choroidal thickness in Japanese schoolchildren: a prospective observational study

Ogawa M, Torii H†, Yotsukura E, Mori K, Hanyuda A, Matsumura J, Fukuoka K, Negishi K, Kurihara T†, Tsubota K†

BMC Ophthalmol. 25 ( 1 ) 300 2025.05

Corresponding author, Accepted

Background: Outdoor activity is important to prevent myopia progression among schoolchildren, and maintaining the choroidal thickness is important to retard myopia progression. However, no research has reported the effects of short-term intensive outdoor activities on the choroidal thickness. This institution-based prospective observational study aims to assess the impact of outdoor activity for 1 week during a camp program to study ocular parameters including the choroidal thickness. Methods: The intensive outdoor activity program included an average of 6.15 ± 2.98 h of daily time spent outdoors during the camp on subsequent days for 1 week at a low-altitude mountain camp. Twenty-four children participated in this program. Results: The main outcome was the change in the choroidal thickness compared with baseline. The data were measured at the beginning and end of the program over the course of 1 week and the changes analyzed. The mean age of the participants (50% female) was 11.5 ± 0.5 (standard deviation) years, and the mean changes were as follows: the refractive error became more positive, the axial length decreased, and the choroidal thickness (µm) increased, respectively, by 0.21 ± 1.35 diopters (P = 0.742), -0.01 ± 0.02 mm (P = 0.241), and 30.7 ± 20.3 μm (P < 0.001). Conclusion: The results suggested that intensive outdoor activity for only 1 week increased the choroidal thickness in Japanese schoolchildren.

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Intraocular Vasculature Formation Precedes Extraocular Vasculature Penetration of Mouse Eyes

Imanishi S., Tomita Y., Negishi K., Tsubota K., Kurihara T†

Dev Biol. 528 https://doi.org/10.1016/j.ydbio.2025.09.010 - 162 2025.05

Last author, Corresponding author, ISSN 00121606

The posterior ocular circulatory system comprises choroidal vasculature and central retinal and posterior ciliary arteries (PCAs) that are fundamental for ocular tissue maintenance. Much is known about the development of the retinal vascular system, but that of the posterior ocular circulation system remain obscure. Therefore, we aimed to clarify the development of the intraocular vasculature involved in the posterior ocular circulation system. Choriocapillaris and hyaloid capillaries are formed in situ and de novo through the endothelial differentiation of hemangioblasts. The intraocular segments of the hyaloid artery penetrate the retina before extraocular segments appear. The intraocular segments of PCAs arise from the hyaloid artery before the extraocular segments reach the eye. The posterior ocular circulation system apparently synchronizes with events throughout the entire process of ocular development. The intraocular vasculature notably formed before the extraocular segments reached the eyes. Our findings provide a novel perspective on ocular development and might facilitate understanding of eye diseases in humans.

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Assessing public awareness of myopia after the COVID-19 pandemic: an infodemiology study

Chen J, Lee D., Ikeda SI, Zhang Y., Negishi K., Tsubota K., Kurihara T†

BMJ Health Care Inform. 32 ( 1 ) e101156 2025.05

Last author, Corresponding author, Accepted

Objectives Since the COVID-19 pandemic started, an increasing number of individuals use online resources to obtain health-related information, including myopia management. We aimed to obtain the search interest of global public health on myopia and prevention/treatment methods before and after the outbreak of COVID-19. Methods Google Trends was used to assess the global search interest in myopia and related terms. Data spanning from 2019 to 2023 were collected and segmented into three periods: prepandemic (2019), pandemic year (2020) and postpandemic (2021-2023). Each average search volume index was used to examine public awareness with the Kruskal-Wallis test. Results Among commonly used search keywords, Myopia is preferred over more colloquial terms (Nearsighted and Shortsighted). During the pandemic, searches for Myopia remained stable, while postpandemic, interest in Myopia surged (31.54%, p<0.0001). Myopia prevention/treatment awareness from 2019 to 2023 indicated notable shifts. In 2020, searches for Contact lenses and Spectacles decreased (-14.09% and -21.97%, respectively, both p<0.0001). These trends persisted postpandemic, with declining searches for Orthokeratology (-41.38%, p<0.01). Public interest for Light therapy (43.00%, p<0.0001) and Atropine (27.42%, p<0.0001) increased. Discussion The research highlights significant increases in global online awareness of myopia during the COVID-19 pandemic. The extended period of remote work during the pandemic may alter lifestyle habits and affect public perception of treatment options. Those findings could offer valuable perspectives on global interest patterns related to myopia, which supports subsequent myopia studies and is further useful to develop relevant public health policies.

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Unilateral Common Carotid Artery Occlusion in Adult Mice with Streptozotocin Comorbidity Leads to Early Retinal Inflammation

Gettinger K*, Lee D*, Negishi K, Kurihara T†

Int J Mol Sci. 26 ( 9 ) 4385 2025.05

Last author, Corresponding author, Accepted, ISSN 16616596

Diabetic retinopathy (DR) is a leading cause of visual impairment. To better understand the pathology, clinically relevant experimental models are needed. Widely used DR models (especially streptozotocin (STZ)-induced) require extended timeframes to reach DR phenotype endpoints and lack ischemic phenotypes, which are in contrast to the human condition. Unilateral common carotid artery occlusion (UCCAO) could provide a retinal ischemic insult. We explored the pathologic synergistic effects of UCCAO in STZ mice. STZ (90 mg/kg) was injected intraperitoneally into adult C57BL/6 mice for three days. Four weeks later, right UCCAO was performed. One week after UCCAO, retinal samples were stained with isolectin B4 to analyze cellular and vascular changes. Retinal samples were obtained one day and one week after UCCAO and quantitative PCR (qPCR) were performed to observe inflammatory and ischemic responses. Only the STZ UCCAO group showed increased inflammatory cells. STZ UCCAO retina demonstrated a significant difference in capillary and large vessel size compared to other groups. At one day and one week, there was a change in mRNA expressions in inflammatory genes Ccl2, Ccl12, Bnip3, Pdk1, Hsp25, and Vegfa in the STZ UCCAO group compared to other groups. Our model can serve as an accelerated DR model for studying inflammatory vascular changes.

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Violet Light Is Abundant Outdoors but Deficient Indoors in Modern Lifestyle in Tokyo

Kondo S*, Jiang X*, Torii H, Mori K, Negishi K, Kurihara T†, Tsubota K†

Int J Enviro Res Public Health. (MDPI AG) 22 ( 3 ) 444 - 444 2025.03

Corresponding author, Accepted, ISSN 16617827

This study examines the role of violet light (VL) in preventing myopia progression, addressing a critical need in urban environments where VL exposure is limited. Recent research suggests that VL, within the 360–400 nm wavelength range, may reduce myopia risk. To investigate, we conducted spectroscopic measurements in various settings across Tokyo, quantifying VL irradiance in natural sunlight. The results showed high VL levels outdoors, averaging 583 μW/cm2 on sunny days and 271 μW/cm2 on cloudy days, leading to a weighted annual average of approximately 310 μW/cm2. In contrast, indoor environments lacked VL due to UV-blocking materials in windows, glasses, and lighting. This deficiency may contribute to the rising incidence of myopia, particularly in urban areas with reduced outdoor exposure. Our findings highlight the need for innovative solutions to mitigate VL deficiency indoors, such as optimizing architectural designs and artificial lighting to better incorporate VL. This study provides foundational insights for future interventions aimed at reducing myopia risk through improved indoor light environments.

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第128回日本眼科学会総会評議員会指名講演II 視覚とニューロサイエンス光生物学を基盤とした眼疾患病態生理の理解と治療開発

栗原俊英

日眼会誌 129 ( 3 ) 354 - 378 2025.03

Lead author, Last author, Corresponding author, Accepted

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