Prolonged Ocular Exposure Leads to the Formation of Retinal Lesions in Mice

Abstract

AbstractThe observation of retinal lesions in the posterior pole of laboratory mice has been found to occur for many reasons, some of which are due to native, developmental abnormalities and those that are influenced by environmental or experimental conditions. Herein, we investigated the rate and extent of retinal lesions as a result of prolonged ocular exposure following general anesthesia. Mice were housed under standard animal care conditions and transported to the laboratory for experimental preparation induction procedures (EPIP) involving general anesthesia, mydriasis/cycloplegia, and topical anesthesia to the cornea. Following EPIP, two ocular recovery conditions (protected and unprotected) were tested within two different animal recovery chambers (open or closed). During anesthesia recovery, and extending up to 2.5 months thereafter, the anterior and posterior poles were evaluated using digital color photography, scanning laser ophthalmoscopy, and spectral-domain optical coherence tomography to document the effects of eye protection and chamber recovery type on the development of retinal lesions. In some mice, electroretinograms and histological evaluations were performed to assess functional and structural changes that accompanied the retinal lesions detected by in vivo imaging. We found that the anterior segments of mice recovered in the open chamber with unprotected eyes showed substantial acute changes. At 1-hour post-EPIP, the anterior chamber exhibited corneal thinning, severe media opacities, a reduction in anterior chamber depth, and ocular lens prolapse. These changes largely resolved upon recovery. At 3- and 14-days post-EPIP, inspection of the posterior pole by fundus imaging revealed prominent lesions in the outer retina in a significant proportion of mice recovered in the open chamber. ERG testing conducted at 1-month post-EPIP revealed compromised functional responses in the eyes of affected vs. unaffected mice. Imaging at 14-days post-EPIP revealed that the outer retina lesions in affected mice almost wholly resolve over time to nearly insignificant levels. However, data collected at 80-days post-EPIP demonstrates that some lingering effects persist long-term and appear to be confined to the retinal pigment epithelium. In comparison, mice recovered in the closed chamber with unprotected eyes experienced only mild lens opacities at 1-hr post EPIP that cleared following a full recovery from the effects of sedation. Furthermore, protected eyes of mice recovered in either the open or closed chamber were completely devoid of any anterior or posterior pole complications. In sum, prolonged ocular surface exposure to circulating ambient room air leads to significant anterior and posterior segment ocular complications. We interpret these changes to be caused by dehydration and desiccation of the corneal surface of the eye. The most abundant, semi-reversible complication observed was the development of lesions in the outer retina, which had a 90% probability of occurring after 45 minutes of exposure. The lesions largely absolved short-term but some imaging evidence suggests that they may persist months after their initial appearance.DisclosuresB.A. Bell, none; V.L. Bonilha, none; S.A. Hagstrom, none; B.Anand-Apte, none; 14 J.G. Hollyfield, none; I.S. Samuels, none.Grant InformationResearch reported in this publication was supported by the National Eye Institute of the National Institutes of Health under award numbers P30EY025585, R01EY016490, RO1EY026181, RO1EY027083, R01EY014240 and R01EY027750, US Dept. of Veterans Affairs Biomedical Laboratory Research and Development Service VA Merit Award I01BX002754, an unrestricted grant from the Research to Prevent Blindness to the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Foundation for Fighting Blindness Research Center Grant, The Wolf Family Foundation, the Llura and Gordon Gund Foundation and the Cleveland Clinic. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the US Dept. of Veterans Affairs.