Retinal ganglion cell degeneration is a characteristic feature of glaucoma, and accordingly, protection of these cells constitutes a major therapeutic objective in the disease. Here, we demonstrate the key influence of caveolin (Cav) in regulating the inner retinal homeostasis in two models of experimentally elevated intraocular pressure (IOP). Two groups of Cav-1^−/− and wild-type mice were used in the study. Animals were subjected to experimentally induced chronic and acutely elevated IOP and any changes in their retinal function were assessed by positive scotopic threshold response recordings. TUNEL and cleaved caspase-3 assays were performed to evaluate apoptotic changes in the retina while Brn3a immunostaining was used as a marker to assess and quantify ganglion cell layer (GCL) changes. H&E staining was carried out on retinal sections to evaluate histological differences in retinal laminar structure. Cav-1 ablation partially protected the inner retinal function in both chronic and acute models of elevated IOP. The protective effects of Cav-1 loss were also evident histologically by reduced loss of GCL density in both models. The phenotypic protection in Cav-1^−/− glaucoma mice paralleled with increased TrkB phosphorylation and reduced endoplasmic reticulum stress markers and apoptotic activation in the inner retinas. This study corroborated previous findings of enhanced Shp2 phosphorylation in a chronic glaucoma model and established a novel role of Cav-1 in mediating activation of this phosphatase in the inner retina in vivo. Collectively, these findings highlight the critical involvement of Cav-1 regulatory mechanisms in ganglion cells in response to increased IOP, implicating Cav-1 as a potential therapeutic target in glaucoma.

视网膜神经节细胞变性是青光眼的特征，因此，保护​​这些细胞构成该疾病的主要治疗目标。在这里，我们证明了在两个实验性升高的眼内压（IOP）模型中小窝蛋白（Cav）在调节内部视网膜稳态方面的关键影响。两组Cav-1 ^-/-在研究中使用了野生型小鼠。使动物经受实验性诱导的慢性和急性IOP升高，并通过阳性暗视阈反应记录评估其视网膜功能的任何变化。进行了TUNEL和裂解的caspase-3分析，以评估视网膜的凋亡变化，而Brn3a免疫染色被用作标记，以评估和量化神经节细胞层（GCL）的变化。对视网膜切片进行H＆E染色以评估视网膜层结构的组织学差异。在慢性和急性IOP升高模型中，Cav-1消融可部分保护视网膜内部功能。Cav-1丢失的保护作用在组织学上也可以通过降低两个模型中GCL密度的丢失来证明。Cav-1中的表型保护^-/-青光眼小鼠与增加的TrkB磷酸化和减少的内质网应激标志物以及内视网膜的凋亡激活平行。这项研究证实了在慢性青光眼模型中增强的Shp2磷酸化的先前发现，并确定了Cav-1在体内磷酸体内介导该磷酸酶活化中的新作用。总的来说，这些发现突显了神经节细胞中Cav-1调节机制的关键参与，以响应增加的IOP，暗示Cav-1作为青光眼的潜在治疗靶点。