To study the macroglia and microglia and the immune role in long-time light exposure in rat eyes, we performed glial cell characterization along the time-course of retinal degeneration induced by chronic exposure to low-intensity light. Animals were exposed to light for periods of 2, 4, 6, or 8 days, and the retinal glial response was evaluated by immunohistochemistry, western blot and real-time reverse transcription polymerase chain reaction. Retinal cells presented an increased expression of the macroglia marker GFAP, as well as increased mRNA levels of microglia markers Iba1 and CD68 after 6 days. Also, at this time-point, we found a higher number of Iba1-positive cells in the outer nuclear layer area; moreover, these cells showed the characteristic activated-microglia morphology. The expression levels of immune mediators TNF, IL-6, and chemokines CX3CR1 and CCL2 were also significantly increased after 6 days. All the events of glial activation occurred after 5–6 days of constant light exposure, when the number of photoreceptor cells has already decreased significantly. Herein, we demonstrated that glial and immune activation are secondary to neurodegeneration; in this scenario, our results suggest that photoreceptor death is an early event that occurs independently of glial-derived immune responses.

The medial part of the nucleus of Edinger–Westphal (EWM) in birds mediates light-regulated adaptive increases in choroidal blood flow (ChBF). We sought to characterize the effect of loss of EWM-mediated ChBF regulation on photoreceptor health in pigeons housed in either moderate intensity diurnal or constant light (CL). Photoreceptor abundance following complete EWM destruction was compared to that following a lesion in the pupil control circuit (as a control for spread of EWM lesions to the nearby pupil-controlling lateral EW) or following no EW damage. Birds were housed post-lesion in a 12 h 400 lux light/12 h dark light cycle for up to 16.5 months, or in constant 400 lux light for up to 3 weeks. Paraformaldehyde–glutaraldehyde fixed eyes were embedded in plastic, sectioned, slide-mounted, and stained with toluidine blue/azure II. Blinded analysis of photoreceptor outer segment abundance was performed, with outer segment types distinguished by oil droplet tint and laminar position. Brains were examined histologically to assess lesion accuracy. Disruption of pupil control had no adverse effect on photoreceptor outer segment abundance in either diurnal light or CL, but EWM destruction led to 50–60% loss of blue/violet cone outer segments in both light conditions, and a 42% loss of principal cone outer segments in CL. The findings indicate that adaptive regulation of ChBF by the EWM circuit plays a role in maintaining photoreceptor health and mitigates the harmful effect of light on photoreceptors, especially short wavelength-sensitive cone photoreceptors.

The question of whether the expression of mutant opsin predisposes the retina to light damage was addressed using transgenic mice that express rhodopsin with three point mutations near the N-terminus of the molecule. The mutations involve the substitution of histidine for proline at position 23 (P23H), glycine for valine at position 20 (V20G), and leucine for proline at position 27 (P27L). These mice express equal amounts of mutant and wild-type transcripts, and develop a progressive photoreceptor degeneration that is similar to that seen in human retinitis pigmentosa (RP). The P23H mutation is associated with the most frequently occurring form of human autosomal dominant retinitis pigmentosa (ADRP) in the United States. Transgenic and normal littermates were exposed to illuminance of 300 foot-candles (ft-c) for 24 h, then placed in darkness for either 6 h, 6 days, or 14 days. Histological and biochemical techniques were used to evaluate the outer retina in light-exposed and control animals reared on 12-h light/12-h dark cycle. The results indicate that light exposure accelerates the pathological changes associated with the transgene expression. Compared with transgenic animals reared in ambient cyclic light, retinas from light-exposed mice had a reduced rhodopsin content, fewer photoreceptor cell bodies, and less preservation of retinal structure. Data obtained from normal mice did not differ for the lighting regimens used. These findings suggest that the expression of VPP mutations in the opsin gene predisposes the transgenic photoreceptors to be more susceptible to light damage. The data also suggest that reducing photic exposure may be beneficial to any patient with RP mediated by an opsin mutation.