Genetic Mutation of mGluR6 Receptor Prevents the Effects Induced by Light Deprivation on the Development of Retinal Ganglion Cells (RGCs)

Abstract

Purpose:: Long-term activation of mGluR6 receptors by intraocular injection of APB or dark rearing retarded the maturational process of RGC dendrites while inactivation of mGluR6 receptors by genetic mutation had no effect on the dendritic morphology of RGCs. These results raised the possibility that altering the synaptic inputs from bipolar cells to RGCs by changing the activation level of mGluR6 receptors on bipolar cells might play an important role in the maturation of RGC dendrites. To test this possibility, we recorded the synaptic inputs of RGCs of wild type (WT) and mGluR6-/- mice and compared the RGC dendritic structures of mGluR6-/- mice raised in the cyclic light and constant darkness.

Methods:: WT, Thy1-YFP-expressing mice and Thy1-YFP/mGluR6-/- mice were used for this study. Normal reared mice were housed in 12:12 hour cyclic light condition and dark reared mice were housed in constant darkness from birth. Spontaneous synaptic inputs of RGCs were recorded from WT and mGluR6-/- retinas using a retinal slice preparation. Three dimensional dendritic structures of RGCs were obtained from YFP-expressing RGCs using a confocal microscope.

Results:: We have three major findings in this study. (1) We found that the rate of spontaneous synaptic inputs to RGCs in mGluR6-/- mice was 6.3-fold higher than that of WT controls. This is opposite to the effect induced by light deprivation on WT mice, which caused more than 60% reduction of RGC synaptic inputs. (2) Mutation of mGluR6 receptors had no significant effect on the development of the dendritic structure of all major morphological types of RGCs. We found that most morphological types of RGCs express YFP in mGLuR6-/- mice. By examining RGC dendritic distribution of mGLuR6-/- mice, we found no significant difference in the number of cells ramified in sublamina a or b of the IPL in comparison with WT mice. (3) In contrast to the WT animals, dark rearing of mGluR6-/- had little effect on the maturation of RGC dendritic structure.

Conclusions:: Our data demonstrated that light deprivation of WT mice reduced the RGC synaptic inputs and retarded the maturation of dendritic structure while genetic mutation of mGluR6 receptor significantly increased the rate of RGC synaptic inputs and completely abolished the effect induced by light deprivation on the maturation of RGC dendritic structure. Therefore, we conclude that the increase of RGC spontaneous synaptic inputs in mGluR6-/- mutants prevents the effects induced by light deprivation on the development of RGC dendritic structure.

Keywords: retina • ganglion cells • development