Photoreceptor outer segment changes observed in rodent models by SDOCT: An early indicator of stress and dysfunction?

Abstract

Purpose : To demonstrate changes observed in the photoreceptor layer by spectral domain optical coherence tomography (SDOCT).

Methods : Various rodent models underwent SLO and SDOCT imaging before and/or after a physiological challenge (i.e. drug, light exposure, diabetes, or aging). In a number of models, B-scan images from the outer retina were compiled and compared to qualitatively demonstrate changes in outer segment (OS) hyper (hyperOS) and hypo (hypoOS) reflectivity. Longitudinal reflectance profiles of the outer retina were analyzed for a change in OS signal slope between affected and unaffected subjects. OS changes were compared to SLO-observed autofluorescent foci, an indicator of sub-retinal inflammatory cells. Retinas were processed for histology and electron microscopy.

Results : Several rodent models exhibited reflectance changes within the proximal outer segment region after both no treatment (baseline findings), or experiments involving acute or chronic stress. Pigmented C57Bl/6J mice exhibited proximal hyperOS changes after pupil dilation and anesthesia induction. Non-pigmented, BALB/cJ and B6(Cg)-Tyr^c-2J/J mice and Spraque-Dawley rats showed hyperOS changes after relocation from dim to standard cyclic light. These changes were observed within days and persisted for many weeks until significant ONL degeneration occurred relative to controls. Evidence of altered photoreceptor morphology could be observed histologically between treatment groups. Several transgenic knockout mice (Cfb, DJ-1, Nyx^nob) displayed HyperOS after several months of aging which were not present at baseline. Two transgenic strains (Collectrin, CCR2) exhibited HyperOS at an earlier age (~3 mos.). Two experiments involving Nyx^nob and C57BL/6J mice suggest that streptozotocin induced diabetes can alter proximal OS architecture in affected mice from hyper or normal reflective, to hyporeflective. All changes were observed in the absence of other abnormal indicators such as aberrant pathology or dystrophy.

Conclusions : This spectrum of examples indicate that reflectivity changes observed within the proximal outer segments are real, quantifiable entities that can provide insight into RPE-Photoreceptor status. Our observations suggest that these changes are induced by one or more physiological stressors that may include hypoxia, ischemia, light exposure, visual cycle dysfunction, oxidation, and hyperglycemia.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.