Recent evidence suggests that melanopsin-expressing intrinsically
photosensitive retinal ganglion cells (ipRGCs), a neuronal class regulating
non-image forming (NIF) vision and generally thought to be injury-resistant,
are dysfunctional in certain neurodegenerative diseases. Although disrupted NIF
visual functions have been reported in patients and animals with diabetes, it
remains controversial whether ipRGCs exhibit remodeling during diabetes and if
so, whether such remodeling is variable among ipRGC subtypes. Here we
demonstrate that survival, soma-dendritic profiles and melanopsin-based
functional activity of M1 ipRGCs were unaltered in streptozotocin-induced 3-month diabetic mice. Such resistance
remained at 6 months after streptozotocin administration. In
contrast, M2/M3 ipRGCs underwent significant remodeling in diabetic mice,
manifested by enlarged somata and increased dendritic branching complexity.
Consistent with the unaltered melanopsin levels, the sensitivity of
melanopsin-based activity was unchanged in surviving M2 cells, but their
response gain displayed a compensatory enhancement. Meanwhile, the pupillary
light reflex, a NIF visual function controlled by M2 cells, was found to be impaired
in diabetic animals. The resistance of M1 cells might be attributed to the
adjacency of their dendrites to capillaries, which makes them less disturbed by
the impaired retinal blood supply at the early stage of diabetes.
Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension
