Elevation of intraocular pressure is a major risk factor for glaucoma development, which causes the loss of retinal ganglion cells (RGCs). Lipocalin 2 (Lcn2) is upregulated in glaucomatous retinae; however, whether Lcn2 is directly involved in glaucoma is debated. In this study, retinal explant cultures were subjected to increased water pressure using a two-chamber culture device, and Lcn2 protein levels were examined by immunoblotting. In situ TdT-mediated dUTP nick and labeling (TUNEL) and glial fibrillary acidic protein (GFAP) immunohistochemical assays were performed to assess apoptosis and gliosis, respectively. The neurotoxicity of Lcn2 in the retinal explant culture was determined with exogenous administration of recombinant Lcn2. The Lcn2 protein levels, percentage of TUNEL-positive cells, and GFAP-positive area were significantly higher in retinae cultured under 50 cm H₂O pressure loads compared to those cultured under 20 cm H₂O. We found that Lcn2 exhibited neurotoxicity in retinae at dose of 1 μg/ml. The negative effects of increased hydrostatic pressure were attenuated by the iron chelator deferoxamine. This is the first report demonstrating the direct upregulation of Lcn2 by elevating hydrostatic pressure. Modulating Lcn2 and iron levels may be a promising therapeutic approach for retinal degeneration.

PURPOSE. Optic nerve crush (ONC) induces retinal ganglion cell (RGC) death, which causes vision loss in glaucoma. To investigate early events leading to apoptosis of RGCs, we performed gene expression analysis of injured retinas in the period before RGC loss. METHODS. The temporal changes of gene profiles at 0, 1, and 4 days after ONC were determined by DNA microarray. To verify the gene expression changes in RGCs, we enriched RGCs by laser-captured microdissection and performed real-time RT-PCR of 14 selected genes. In situ localization study was performed by immunohistochemistry. RESULTS. At 1 day and 4 days after ONC, 1423 and 2010 retinal genes were changed compared with 0 day, respectively these genes were mainly related to apoptotic process, immune process, regulation of cell cycle, and ion transport. RT-PCR analysis revealed that expression levels of Activating transcription factor 3 (Atf3), Lipocalin 2 (Lcn2), and tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) were remarkably changed in RGC-enriched fraction within 4 days postcrush. Immunohistochemical analysis confirmed that all of these genes expressed highly in the ganglion cell layer of crushed retinas. CONCLUSIONS. In response to ONC, the expression of apoptotic genes was stimulated soon after crush. Atf3, Lcn2, and Tnfrsf12a might be key molecules responsible for RGC loss in glaucoma.

目的:前部円錐水晶体を伴ったAlport症候群に対して水晶体再建術を行った報告。症例:46歳,男性。8ヵ月前に両眼の視力低下を自覚して受診した。慢性腎不全と難聴の既往があり,長女がAlport症候群で治療中であった。母親に血尿が認められていた。初診時の視力は左右とも0.07(0.3)で,両眼に前部円錐水晶体を認めたため,水晶体再建術を施行した。術中は,前嚢は薄く伸展性に富み,continuous curvicular capsulotomyが困難であった。切除した前嚢の組織像では,全層にわたり微細な亀裂が認められた。術後の矯正視力は右(1.0),左(0.9)で,その後3年間視力を維持している。結論:Alport症候群に合併した前部円錐水晶体による視力低下に対し,水晶体再建術を施行した結果,視機能の改善を得た。(著者抄録)

緒言：Alport症候群とは，IV型コラーゲンα鎖遺伝子の遺伝的欠損に起因する進行性遺伝性糸球体腎炎であり，10~20％に眼症状を伴う．今回、前部円錐水晶体を合併して手術を施行したAlport症候群の1例を経験したので報告する． 症例：46歳の男性．2009年9月より急速な視力低下を自覚し，同年12月に近畿大学眼科を紹介された．既往症は慢性腎不全と難聴があり，家族歴は娘にAlport症候群があった．初診時の視力は右0.07（0.3×S-8.00D=C-2.25D Ax160°），左0.07（0.3×S－7.00D=C-2.75D Ax20°）で，細隙灯顕微鏡検査で両眼に水晶体前面の突出を認めたが白内障は軽度であった．眼底は両眼に網膜変性があった．以上の所見から，視力低下の原因はAlport症候群に合併した前部円錐水晶体に起因する不正乱視によるものと診断し，同年9月に両眼の水晶体乳化吸引術＋眼内レンズ挿入術を施行した．術中所見では，前嚢が非常に薄く，C.C.C.が困難であった．術後の視力は右0.9（1.0×S+1.00D=C-1.75D Ax130°），左0.5（0.9×S

Alport症候群とは，IV型コラーゲンα鎖遺伝子の遺伝的欠損に起因する進行性遺伝性糸球体腎炎であり，10~20％に眼症状を伴う．今回、前部円錐水晶体を合併して手術を施行したAlport症候群の1例を経験したので報告する． 症例：46歳の男性．2009年9月より急速な視力低下を自覚し，同年12月に近畿大学眼科を紹介された．既往症は慢性腎不全と難聴があり，家族歴は娘にAlport症候群があった．初診時の視力は右0.07（0.3×S-8.00D=C-2.25D Ax160°），左0.07（0.3×S－7.00D=C-2.75D Ax20°）で，細隙灯顕微鏡検査で両眼に水晶体前面の突出を認めたが白内障は軽度であった．眼底は両眼に網膜変性があった．以上の所見から，視力低下の原因はAlport症候群に合併した前部円錐水晶体に起因する不正乱視によるものと診断し，同年9月に両眼の水晶体乳化吸引術＋眼内レンズ挿入術を施行した．術中所見では，前嚢が非常に薄く，C.C.C.が困難であった．術後の視力は右0.9（1.0×S+1.00D=C-1.75D Ax130°），左0.5（0.9×S+1.25D=C-