Neuroprotection of the Inner Retina Also Prevents Secondary Outer Retinal Pathology in a Mouse Model of Glaucoma.
Neuroprotection of the Inner Retina Also Prevents Secondary Outer Retinal Pathology in a Mouse Model of Glaucoma.
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DOI：
10.1167/iovs.62.9.35
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发表时间：
2021-07-01
影响因子：
4.4
通讯作者：
Bloomfield SA
中科院分区：
文献类型：
--
作者：
Kumar S;Ramakrishnan H;Viswanathan S;Akopian A;Bloomfield SA
我们检查了青光眼小鼠模型外层视网膜的结构和功能变化。我们研究了这些变化是否是内层视网膜损伤的继发性后果，以及内层视网膜的神经保护是否也可以防止外层视网膜的变化。我们使用了一个已建立的青光眼微珠阻塞模型，其中眼内压（IOP）升高。特异性抗体用于标记视杆和视锥双极细胞（BC）、水平细胞（HC）和视网膜神经节细胞（RGC），以及对照眼和昏迷眼中的突触组分，以评估结构损伤和细胞损失。进行ERG记录以评估外视网膜功能。我们发现，在IOP升高后，BCs的结构和功能受损，包括显著的细胞丢失和HC的树突/轴突重塑。在微珠注射后4至5周，两种BC的第一次显著损失发生。然而，在3周时观察到RGCs树突状结构的早期变化，但直到4周才观察到杆状BC轴突末端结构的显著变化。我们发现，通过药物阻断缝隙连接或基因切除连接蛋白36来保护青光眼眼内视网膜神经元在很大程度上防止了外视网膜损伤。总之，我们的研究结果表明青光眼的外视网膜损伤是内视网膜原发性损伤的继发性后遗症。内视网膜的神经保护也可以防止外视网膜损伤的发现对于有效的神经保护治疗的靶点具有重要意义。
We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also prevents outer retinal changes. We used an established microbead occlusion model of glaucoma whereby intraocular pressure (IOP) was elevated. Specific antibodies were used to label rod and cone bipolar cells (BCs), horizontal cells (HCs), and retinal ganglion cells (RGCs), as well as synaptic components in control and glaucomatous eyes, to assess structural damage and cell loss. ERG recordings were made to assess outer retina function. We found structural and functional damage of BCs, including significant cell loss and dendritic/axonal remodeling of HCs, following IOP elevation. The first significant loss of both BCs occurred at 4 to 5 weeks after microbead injection. However, early changes in the dendritic structure of RGCs were observed at 3 weeks, but significant changes in the rod BC axon terminal structure were not seen until 4 weeks. We found that protection of inner retinal neurons in glaucomatous eyes by pharmacological blockade of gap junctions or genetic ablation of connexin 36 largely prevented outer retinal damage. Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.
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影响因子：
4.4
作者：
Fernandez-Sanchez, Laura;de Sevilla Mueller, Luis Perez;Cuenca, Nicolas
通讯作者：
Cuenca, Nicolas
影响因子：
3.4
作者：
Cuenca, Nicolas;Pinilla, Isabel;Vidal-Sanz, Manuel
通讯作者：
Vidal-Sanz, Manuel
影响因子：
3.4
作者：
Bosco A;Breen KT;Anderson SR;Steele MR;Calkins DJ;Vetter ML
通讯作者：
Vetter ML
影响因子：
3.7
作者：
Cifuentes-Canorea P;Ruiz-Medrano J;Gutierrez-Bonet R;Peña-Garcia P;Saenz-Frances F;Garcia-Feijoo J;Martinez-de-la-Casa JM
通讯作者：
Martinez-de-la-Casa JM
影响因子：
16.2
作者：
Deans, MR;Volgyi, B;Paul, DL
通讯作者：
Paul, DL