Papers - Kurihara, Toshihide

SOCS3 is required to temporally fine-tune photoreceptor cell differentiation

Ozawa, Yoko, Nakao, Keiko, Shimazaki, Takuya, Shimmura, Shigeto, Kurihara, Toshihide, Ishida, Susumu, Yoshimura, Akihiko, Tsubota, Kazuo, Okano, Hideyuki

DEVELOPMENTAL BIOLOGY (ACADEMIC PRESS INC ELSEVIER SCIENCE)  303 ( 2 ) 591 - 600 2007.03

Research paper (scientific journal), Accepted,  ISSN  0012-1606

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Suppressor of cytokine signaling 3 (SOCS3) is an intracellular, ligand-induced negative feedback modulator of STAT3 activation that acts during inflammation. Here, we dernonstrate that SOCS3 expression is important for normal retinal development in the perinatal period. STAT3 is highly activated in the late-embryonic retina, then downregulated at postnatal day 0 (PO), presumably by the depletion of upstream ligands. We found that SOCS3 was required after PO to shut down the residual STAT3 activation; this loss of activated STAT3 leads to Rhodopsin expression and rod photoreceptor cell differentiation. SOCS3 deficiency failed to terminate STAT3 activation, thereby delaying expression of Rhodopsin and its upstream transcription factor, crx. Development subsequently continued, but its course was temporally erratic, probably because of faulty compensation. Interestingly, SOCS3 protein expression was first detected postnatally, after STAT3 activation was mostly downregulated. It initially appeared in some of the presumptive photoreceptor cells and gradually spread. SOCS3 mRNA level was constant from the late-embryonic to early-postnatal period. Post-transcriptional inhibition of SOCS3 protein expression maintains a high STAT3 activation during late embryogenesis, and after PO, releasing from the inhibition promptly terminates STAT3 activation. Thus, SOCS3 can act as a temporal fine-tuner of STAT3 activation during photoreceptor cell differentiation. (c) 2006 Elsevier Inc. All rights reserved.

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Neuroprotective effects of angiotensin II type 1 receptor (AT1R) blocker, telmisartan, via modulating AT1R and AT2R signaling in retinal inflammation

Kurihara, Toshihide, Ozawa, Yoko, Shinoda, Kei, Nagai, Norihiro, Inoue, Makoto, Oike, Yuichi, Tsubota, Kazuo, Ishida, Susumu, Okano, Hideyuki

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (ASSOC RESEARCH VISION OPHTHALMOLOGY INC)  47 ( 12 ) 5545 - 5552 2006.12

Research paper (scientific journal), Accepted,  ISSN  0146-0404

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PURPOSE. To investigate the retinal neural damage that occurs during inflammation and the therapeutic effects of the angiotensin II type 1 receptor (AT1R) blocker, telmisartan, using a model of endotoxin- induced uveitis (EIU).
METHODS. The localization of AT1R and AT2R was shown by immunohistochemistry. EIU was induced by intraperitoneal injection of lipopolysaccharide (LPS). Animals were treated with telmisartan for 2 days and were evaluated 24 hours later. Expression levels of angiotensin II, STAT3 activation induced by inflammatory cytokines, and retinal proteins essential for neural activities (e. g., synaptophysin, rhodopsin) were analyzed by immunoblot. An AT2R antagonist was administered to evaluate the contribution of AT2R signaling in this therapy. Dark-adapted full-field electroretinography ( ERG) was also performed.
RESULTS. AT1R and AT2R were expressed in presynaptic terminals in most of the retinal neurons. AT1R was also expressed in Muller glial cells. During inflammation, angiotensin II expression was elevated, STAT3 was activated, and synaptophysin and rhodopsin expression were reduced. The expression of glial fibrillary acidic protein (GFAP), downstream of STAT3 activation, was induced in Muller glial cells. However, treatment with telmisartan successfully avoided all these changes. An AT2R antagonist lowered synaptophysin expression despite the treatment. STAT3 activity was negatively correlated with rhodopsin expression. Furthermore, ERG responses, which were mostly prevented by telmisartan, were disturbed during inflammation.
CONCLUSIONS. Retinal protein expression and visual function are both disturbed by inflammation. Treatment with the AT1R blocker telmisartan efficiently prevented these signs of retinal neural damage through the reduction of local angiotensin II expression, the blockade of AT1R, and the relative upregulation of AT2R function.

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Pars plana vitrectomy with internal limiting membrane removal for macular hole associated with proliferative diabetic retinopathy.

Kurihara T, Noda K, Ishida S, Inoue M†

Graefes Arch Clin Exp Ophthalmol. (SPRINGER)  243 ( 7 ) 724 - 726 2005.01

Lead author, Accepted,  ISSN  0721-832X

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Background: We describe the outcome of vitreous surgery in three eyes of three patients with macular hole associated with proliferative diabetic retinopathy (PDR) in the absence of fibrovascular proliferation, a combination of conditions where efficacy is incompletely known. Methods: The patients, all male were 62, 65, and 66 years old. Panretinal photocoagulation had been performed preoperatively in all, and one eye had undergone vitreous surgery. No fibrovascular tissue causing macular traction was observed in any case. Fluorescein angiography and optical coherence tomography (OCT) demonstrated persistent diabetic macular edema surrounding the hole. Affected eyes were treated with vitrectomy including internal limiting membrane (ILM) peeling; 20% sulfur hexafluoride gas (SF6) was introduced for tamponade. Results: Anatomical closure of the macular hole as well as resolution of macular edema was achieved in all cases, and vision improved considerably by more than two Snellen lines. Conclusions: Vitreous surgery with ILM peeling was effective for macular hole associated with PDR, attaining not only macular hole closure but also resolution of persistent diabetic macular edema.

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A case of retinal detachment associated with acquired retinoschisis and macular pucker

Toshihide Kurihara, Hajime Shinoda, Tadahiko Eshita, Shizuaki Kitamura, Kei Shinoda, Makoto Inoue, Masaro Ogata

Japanese Review of Clinical Ophthalmology 98 ( 3 ) 205-208 - 208 2004.03

Research paper (scientific journal), Joint Work