Chronic Antioxidant Capacity Loss in Anterior Chamber Environment After Iridectomy.

Purpose: To compare the ascorbic acid concentration and total antioxidant capacity in the aqueous humor of pigmented Rex rabbits after sham operation (control), iridectomy, and trabeculectomy. Methods: Pigmented Rex rabbits were divided into control, iridectomy, and trabeculectomy groups and followed up for 12 months after surgery. Ascorbic acid concentration and total antioxidant capacity in the aqueous humor, intraocular pressure, and the occurrence of cataracts were examined in each group. Results: The ascorbic acid concentration and total antioxidant capacity after iridectomy and trabeculectomy were significantly lower at one week and at one, six, and 12 months after operation than those in the control group (P ≤ 0.03). Ascorbic acid concentration was positively and significantly correlated with total antioxidant capacity in the aqueous humor (P < 0.01). Compared to the control and the iridectomy groups, intraocular pressure in the trabeculectomy group was significantly lower at one week and at one and six months after surgery (one week: P < 0.01 and P < 0.01, respectively; one month: P < 0.01 and P = 0.03, respectively; six months: P = 0.03). Histological findings in the iridectomy and trabeculectomy groups included the appearance of vacuoles in the lens at six and 12 months after surgery. Conclusions: Iridectomy causes a sustained decrease in ascorbic acid concentration, followed by a long-term decrease in the total antioxidant capacity within the aqueous humor. Translational Relevance: The animal model possibly predicts the vulnerability focusing on the antioxidant level in the anterior chamber environment after trabeculectomy and iridectomy per se in clinical settings.

Gene expression profile analysis of the rabbit retinal vein occlusion model.

The rabbit retinal vein occlusion (RVO) model is an experimental system that mimics retinal ischemic diseases in humans. The rabbit RVO model is widely used to assess the therapeutic efficacy of various experimental surgical procedures. In the present study, we measured temporal retinal expression of Vegfa, which is known as an ischemic response gene, in rabbit RVO. This analysis revealed that the retinal Vegfa transcriptional response began 7 days after generation of RVO, rather than immediately after induction of ischemia. Next, in order to analyze ischemia-induced changes in gene expression profiles, we performed microarray analysis of day 7 RVO retina versus control retina. The angiogenic regulators Dcn and Mmp1 and pro-inflammatory factors Mmp12 and Cxcl13 were significantly upregulated in RVO retinas. Further, we suggest that epigenetic regulation via the REST/cofactor-complex could contribute to RVO pathology. Among human homologous genes in rabbits, genes associated with hypoxia, angiogenesis, and inflammation were significantly upregulated in RVO retinas. Components of the Tumor necrosis factor-alpha (TNFα) and Nuclear factor-kappa B (NF-κB) pathways, which play regulatory roles in angiogenesis and inflammation, were significantly upregulated in RVO, and the expression levels of downstream factors, such as the transcription factor AP-1 and chemokines, were increased. Further, connectivity map analyses suggested that inhibitors of the NF-κB pathway are potential therapeutic agents for retinal ischemic disease. The present study revealed new insights into the pathology of retinal ischemia using the rabbit RVO model, which accurately recapitulates human disease.