Abstract
Purpose: :
To investigate the effect of intravitreous injections of triamcinolone (TA) on intravitreous neovascularization (IVNV) and existing intraretinal vascularization using a rat model of oxygen induced retinopathy (OIR).
Methods: :
Newborn Sprague–Dawley rats and their mothers were placed in an Oxycycler (Biospherix, NY). Oxygen was cycled between 10 and 50% every 24 hours. At p14, rats were removed from the cycler and given a 1µL intravitreous (IV) injection of TA (15, 30 or 60µg/µL) or sterile PBS. TA was washed before injection by replacing supernatant with PBS after centrifugation. After 4 days in room air, rats were euthanized and perfused with 4% paraformaldehyde before the eyes were removed. Following dissection, retinas were flat–mounted and stained with TRITC conjugated Griffonia lectin and caspase–3. IVNV was quantified by counting clock hours (CH), and percent peripheral avascular area of each retina was determined. Central capillary density was quantified by counting vessel junctions within a fixed retinal area. Vessel tortuosities of major posterior pole arteries and veins were measured using vessel extraction software developed at UNC’s Computer Aided Diagnosis and Display Lab.
Results: :
Clock hours of IVNV were significantly reduced for each dose of TA vs. non–injected eyes (6.6 ± 2.7, 5.5 ± 3.3, 5.2 ± 3.5 vs. 8.8 ± 2.1, p<0.020, p<0.001, p<0.001, students T–Test, 15, 30, 60µg/µL vs. non–injected respectively). Central capillary density was significantly reduced in 30µg/µL injected eyes vs. non–injected eyes (157 ± 50 vs. 286 ± 77 junctions per 0.64mm^2, p<0.016, students T–Test) and in 60µg/µL injected eyes vs. non–injected eyes (137 ± 29 vs. 286 ± 77 junctions per 0.64mm^2, p<0.009, students T–Test), but not in the 15µg/µL injected eyes. Qualitative analysis of caspase–3 images indicated no increase in apoptosis in each TA treatment group vs. untreated eyes. There were no significant differences in total retinal area, percent peripheral avascular areas, or vessel tortuosities across treatment groups.
Conclusions: :
High doses of TA reduce IVNV in an OIR rat model but also reduce central capillary density, which requires further study to understand the mechanism and determine possible concerns with safety.
Keywords: proliferative vitreoretinopathy • retinal neovascularization • drug toxicity/drug effects