Light-evoked S-nitrosylation in the retina

Area of Science:

• Neuroscience
• Biochemistry
• Vision Science

Background:

• Nitric oxide (NO) modulates visual processing in the retina via soluble guanylate cyclase.
• NO can also modify proteins directly through S-nitrosylation, a process not considered significant in the central nervous system under physiological conditions.

Purpose of the Study:

• To investigate the extent and significance of S-nitrosylation in the retina under physiological light stimulation.
• To determine if light-evoked NO production leads to S-nitrosylation of retinal proteins.

Main Methods:

• Immunohistochemistry in goldfish and mouse retinas.
• Inhibition of S-nitrosylation using N-ethylmaleimide (NEM) and neuronal NO synthase (NOS) using 1-(2-trifluromethylphenyl)imidazole (TRIM).
• Analysis of retinas from transgenic mice lacking neuronal NOS.
• Mass spectrometry to identify S-nitrosylated proteins.

Main Results:

• Extensive S-nitrosylation of retinal proteins was observed in goldfish and mice under physiologically relevant light intensities, in an intensity-dependent manner.
• Light-evoked S-nitrosylation was abolished by NEM, TRIM, and in neuronal NOS-deficient mice.
• Mass spectrometry identified over 300 S-nitrosylated proteins in light-adapted mouse retinas, many involved in retinal signal processing.

Conclusions:

• Light-evoked nitric oxide production in the retina leads to extensive S-nitrosylation.
• S-nitrosylation is a significant physiological post-translational modification affecting numerous proteins involved in retinal function.