High-Fat Diet Alters the Retinal Transcriptome in the Absence of Gut Microbiota.

The relationship between retinal disease, diet, and the gut microbiome has shown increasing importance over recent years. In particular, high-fat diets (HFDs) are associated with development and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy. However, the complex, overlapping interactions between diet, gut microbiome, and retinal homeostasis are poorly understood. Using high-throughput RNA-sequencing (RNA-seq) of whole retinas, we compare the retinal transcriptome from germ-free (GF) mice on a regular diet (ND) and HFD to investigate transcriptomic changes without influence of gut microbiome. After correction of raw data, 53 differentially expressed genes (DEGs) were identified, of which 19 were upregulated and 34 were downregulated in GF-HFD mice. Key genes involved in retinal inflammation, angiogenesis, and RPE function were identified. Enrichment analysis revealed that the top 3 biological processes affected were regulation of blood vessel diameter, inflammatory response, and negative regulation of endopeptidase. Molecular functions altered include endopeptidase inhibitor activity, protease binding, and cysteine-type endopeptidase inhibitor activity. Human and mouse pathway analysis revealed that the complement and coagulation cascades are significantly affected by HFD. This study demonstrates novel data that diet can directly modulate the retinal transcriptome independently of the gut microbiome.

Use of a Juvenile Rabbit Animal Model to Evaluate Therapeutic Interventions for Postoperative Inflammation and Fibrin Formation After Lensectomy.

PURPOSE: We used the juvenile rabbit as a model for investigating therapeutic interventions for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion for management of pediatric cataracts. METHODS: Twelve 6- to 7-week-old, 600 to 900 g rabbits underwent bilateral clear-cornea lensectomy via irrigation and aspiration with IOL insertion. Following wound closure, enoxaparin 8 mg (n = 6 eyes), preservative-free triamcinolone 0.5 mg (n = 6), 8 mg enoxaparin plus 0.5 mg triamcinolone (n = 6), or balanced salt solution (n = 6) was injected into the anterior chamber. Slit-lamp examinations and optical coherence tomography (OCT) scans were performed postoperatively on days 3 through 7, and 14 to characterize levels of inflammation and fibrin. Using 17 additional rabbits, enzyme-linked immunosorbent assays (ELISAs) with 100 µL of aqueous humor were performed to quantify the amount of fibrinogen and fibrin preoperatively and on postoperative day 3. Immunohistochemistry was performed to confirm the presence of fibrin. RESULTS: Enoxaparin alone and combined with triamcinolone reduced the amount of fibrin present in the anterior chamber compared to untreated eyes, which corresponded to an increase in OCT signal strength. Despite the clear visual axis shown in clinical images, the combination treatment group had the highest levels of soluble fibrin when assessed by ELISA. Immunohistochemistry confirmed the presence of insoluble fibrin seen clinically. CONCLUSIONS: A combination of enoxaparin and triamcinolone appears to provide the most therapeutic benefit by reducing fibrin formation and postoperative inflammation. TRANSLATIONAL RELEVANCE: The juvenile rabbit is an excellent model to investigate inflammation and fibrin formation following lensectomy with IOL insertion and possibly any intraocular surgery in children.