Functional and neurochemical development in the normal and degenerating mouse retina

Abstract

The rd1 mouse is a well-established animal model for human retinitis pigmentosa (RP). We used electroretinography (ERG) to evaluate retinal function and postembedding immunocytochemistry to determine the changes in cellular amino acid expression in the normal (C57Bl6) and degenerating mouse retina (rd1), as a function of age during development and the onset of degeneration. In the normal mouse retina, photoreceptoral and post-photoreceptoral ERG responses improved simultaneously from eye-opening until adult levels were achieved at approximately postnatal day (P) 30. Maturation of amino acid neurochemistry preceded the development of retinal function in the normal retina. Amino acid levels increased immediately from birth and reached stable levels by eye-opening. In contrast, in the rd1 mouse, both rod and cone pathway function rapidly reduced from eye-opening and by P21 became undetectable. Interestingly, at P18 cone responses were still comparable between the normal and degenerating retina. Before eye opening, the pattern of amino acid immunoreactivity in the rd1 retina was similar to the normal retina. Alterations in neurochemistry were observed after the onset of rod photoreceptor cell death. The most obvious change was the reduction in neurotransmitter immunoreactivity within the synaptic layers and some cell classes of the rd1 retina. Reduction of glutamine and glutamate was observed in Müller cells before established gliosis markers. Overall, these results suggest the rapid maturation of neurochemistry by eye opening followed by functional maturation by P30 in the normal retina. The dystrophic retina displays similar neurochemistry to control retina before eye opening but a subsequent decline. J. Comp. Neurol. 521:1251-1267, 2013

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

“…In rd1 mice, the ERG response begins to reduce after eye opening, and becomes undetectable at around P21 [29]. In this study, we found that at P18, the normal ERG of C57 mice could be detected (Fig.…”

“…1E). In rd1 mice, the apoptosis of rod cells usually appears at P8 and peaks at P14 [29, 30]. In this study, the number of apoptotic cells in the ONL of DMSO-treated rd1 mice at P14 significantly increased compared with age-matched C57 mice (P<0.001; Fig.…”

“…2E, F). The ERGs of rd1 mice are nearly undetectable at low light intensity [29]. We found that DMSO-treated rd1 mice at P18 showed no amplitude of a- or b- waves (Fig.…”

“…Different from P23H mutation rats, retinal degeneration 1 (rd1) mice harbor a mutation that affects the expression of phosphodiesterase 6 beta subunit (PDE6β), resulting in the accumulation of cyclic guanosine monophosphate (cGMP), and ultimately, a reduction in the number of rod cells. Activation of microglia in the retina of rd1 mice plays an important role in the apoptosis of photoreceptors, which eventually affects the visual function of the retina [29, 30]. It remains unclear if curcumin delays the rapid degeneration of photoreceptors in rd1 mice or inhibits the activation of microglia and regulates the secretion of inflammatory cytokines.…”

Sildenafil alters retinal function in mouse carriers of Retinitis Pigmentosa

“…3). To determine the relationship between photoreceptors and inner retinal neurons, the ratio of the b-wave to a-wave amplitude at the highest light intensity was determined for each individual animal then presented as the mean ± SEM (Gibson et al, 2013). Representative ERG traces before (grey line) and 1 h after (black line) administration of 5Â (7.25 mg/kg), 10Â (14.5 mg/kg) or 50Â (72.5 mg/kg) the normal maximum sildenafil dose.…”