Long-term ERG analysis in the partially light-damaged mouse retina reveals regressive and compensatory changes

Abstract

Most of the blinding retinopathies are due to progressive photoreceptor degeneration. Treatment paradigms that are currently being investigated include strategies to either halt or slow down photoreceptor cell loss, or to replace useful vision with retinal prosthesis. However, more information is required on the pathophysiological changes of the diseased retina, in particular the inner retina, that occur as a consequence of photoreceptor cell loss. Here we wished to use light damage as a stoppable insult to determine the structural and functional consequences on inner and outer retina, with the overall goal of determining whether survival of a functional inner retina is possible even if the outer retina is damaged. Mice were exposed to a 20-day light-damage period. Electroretinograms (ERG) and morphology were used to assess subsequent recovery. Outer retina was monitored analyzing a-waves, which represent photoreceptor cell responses, and histology. Integrity of the inner retina was monitored, analyzing b-waves and oscillatory potentials (OP1-OP4) and immunohistochemical markers for known proteins of the inner retina. All six ERG components were significantly suppressed with respect to amplitudes and kinetics, but stabilized in a wave-dependent manner within 40-70 days after the end of light exposure. As expected, damage of the outer retina was permanent. However, function of the inner retina was found to recover significantly. While b-wave amplitudes remained suppressed to 60% of their baseline values, OP amplitudes recovered completely, and implicit times of all components of the inner retina (b-wave and OP1-OP4) recovered to a level close to baseline values. Histological analyses confirmed the lack of permanent damage to the inner retina. In summary, these data suggests that the inner retina has the potential for significant recovery as well as plasticity if treatment is available to stop the deterioration of the outer retina.

Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy

“…In fact, the increase in b-wave/a-wave amplitude implies that the inner retina increased its sensitivity in response to a loss of input from photoreceptors. Similar sensitivity increase in the inner retina has been observed in mild-to-intermediate level photoreceptor degenerations induced by bright light exposure in mice and rats 41–43 . The increase in inner retina sensitivity might result from synaptic strengthening between the remaining photoreceptors and inner retinal cells 42 .…”

Eliminating Complement Factor D Reduces Photoreceptor Susceptibility to Light-Induced Damage

“…29 Given sufficient time for the retina to stabilize, the ERG waves will recover. 30 However, the possibility that the small reduction in photoreceptor activity prior to light damage could blunt the sensitivity of the photoreceptors to light damage requires consideration. Hao et al 25 have shown that the kinetics by which bleached rhodopsin is regenerated, and thus how much pigment is available for bleaching at any given time, dictates the cell's sensitivity to light-induced photoreceptor degeneration.…”

Estrogen Ameliorates Photoreceptor Cell Loss In Light-Induced Retinal Degenerated Balb/C Mice

“…In mice, color vision is mediated by cone photoreceptors, which comprises about 3-5% of cells in the outer nuclear layer [19].…”

“…ERG recordings were performed as described previously [19]. In short, mice were dark adapted overnight.…”