Effects of D-serine treatment on outer retinal function

• Published in: Experimental eye research Vol. 211; p. 108732
• Main Authors: Torres Jimenez, Nathalia, Miller, Robert F., McLoon, Linda K.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2021
• Subjects: A-wave; B-wave; D-serine; Electroretinogram; Mesopic; Mice; A-wave; Mice; D-serine; Electroretinogram; B-wave; Mesopic
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2021.108732

The role of the N-Methyl-D-Aspartate Receptor (NMDAR) in the outer retina is unclear despite expression of the NMDAR-complex and its subunits in the outer retina. The flash-electroretinogram (fERG) offers a non-invasive measurement of the retinal field potentials of the outer retina that can serve to clarify NMDAR contribution to early retinal processing. The role of the NMDAR in retinal function was assessed using a genetic mouse model for NMDAR hypofunction (SR-/-), where the absence of the enzyme serine racemase (SR) results in an 85% reduction of retinal D-serine. NMDAR hypo- and hyperfunction in the retina results in alterations in the components of the fERG. The fERG was examined after application of exogenous D-serine to the eye in order to determine whether pre- and post-topical delivery of D-serine would alter the fERG in SR-/- mice and their littermate WT controls. Amplitude and implicit time of the low-frequency components, the a- and b-wave, were conducted. Reduced NMDAR function resulted in a statistically significantly delayed a-wave and reduced b-wave in SR-/- animals. The effect of NMDAR deprivation was more prominent in male SR-/- mice. A hyperfunction of the NMDAR, through exogenous topical delivery of 5 mM D-serine, in WT mice caused a significantly delayed a-wave implicit time and reduced b-wave amplitude. These changes were not observed in female WT mice. There were temporal delays in the a-wave and amplitude and a decrease in the b-wave amplitude and implicit time in both hypo- and NMDAR hyperfunctional male mice. These results suggest that NMDAR and D-serine are involved in the retinal field potentials of the outer retina that interact based on the animal's sex. This implicates the involvement of gonadal hormones and D-serine in retinal functional integrity. •Alteration in D-serine levels result in changes to the flash electroretinogram.•Reduced D-serine levels resulted in delayed a-waves and reduced b-waves.•These changes were sex-specific and only seen in male mice.•Gonadal hormones and D-serine play a role in retinal function integrity.