Abstract
Purpose: :
The developing mammalian retina is highly plastic. Shortfalls of a single cell type are often compensated by modification of other cell types. Here, we examined how developing cone bipolar cells (CBCs) respond to retinal ganglion cell (RGC) shortage. Furthermore, we examined the importance of bipolar cell function in maintaining the retinal integrity.
Methods: :
We use Math5 –/– mice, which generate only 5% of RGCs during retinogenesis, to analyze the CBC response to RGC shortage. The CBC morphology was analyzed by recoverin and LacZ labeling in Math5–/– and Math5–/–/Vsx1τLacz/+ retina respectively. Math5–/–/Vsx1–/– retinas were used to further study the retinal responses in an RGC–deprived environment while CBC cannot fully function. Modifications of cell populations and morphologies were studied by immunostaining using varies antibodies.
Results: :
In retinas (Math5–/–) that 95% of RGCs were missing during retinogenesis, the recoverin positive CBCs showed expanded axonal fields compared to those in a normal retina. The inner nuclear layer (INL) of the Math5/Vsx1–deficient retina endured dramatic cell loss compared to that of a Math5–deficient retina which cell loss in the INL was minor. ChAT–, Calbindin–, Calretinin–, Glutamin synthetase– and PKCα–positive cells were found in the extremely thin INL of the Math5/Vsx1–deficient retinas.
Conclusions: :
The results showed that CBCs modify their axonal fields in response to RGC shortage. Our data indicates that cone bipolar cells, rod bipolar cells, starburst amacrine cells, and Müller cells remained in the one cell layer thin INL in the Math5/Vsx1–deficient retina. Thinning of the INL may not due to a specific cell type loss in the INL. Our results suggest that CBC axonal modification as well as normal CBC function are important to sustain the INL integrity in a challenged retinal environment.
Keywords: retinal development • plasticity • bipolar cells