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Publication : Age- and Sex-Specific Regulation of Serine Racemase in the Retina of an Alzheimer's Disease Mouse.

First Author  Wang Y Year  2025
Journal  Invest Ophthalmol Vis Sci Volume  66
Issue  1 Pages  36
PubMed ID  39813057 Mgi Jnum  J:361435
Mgi Id  MGI:7858131 Doi  10.1167/iovs.66.1.36
Citation  Wang Y, et al. (2025) Age- and Sex-Specific Regulation of Serine Racemase in the Retina of an Alzheimer's Disease Mouse. Invest Ophthalmol Vis Sci 66(1):36
abstractText  PURPOSE: Changes associated with Alzheimer's disease (AD) may have measurable effects on the retina, which may facilitate early detection due to the eye's accessibility. Retinal pathology and the regulation of serine racemase (SR) were investigated in the retinas of APP(SW)/PS1(E9) mice. METHODS: SR in the retinas and the content of D-serine in the aqueous humor were analyzed. The structure and function of the retina were assessed. Additionally, the regulation of SR in primary Muller cell cultures was investigated. RESULTS: SR levels were significantly higher in the retinas of 18- and 24-month-old male APP/PS1 mice, whereas aqueous humor D-serine was lower in 24-month-old APP/PS1 male mice compared to wild-type (WT) mice. Neither Abeta nor 17beta-estradiol increased SR, but the combination of both did in Muller cell cultures. In contrast, 17beta-estradiol increased Srr mRNA in the cultures. At 8 months of age, male APP/PS1 mice began to display reduced b-wave amplitude in scotopic and photopic electroretinography (ERG) recordings, unlike female APP/PS1 mice. Although the retinal layer thickness in APP/PS1 mice did not differ from WT mice, there was overt apoptosis in the inner and outer nuclear layers of the APP/PS1 mice retinas. CONCLUSIONS: The age- and sex-specific regulation of SR is correlated with the pathology of an AD retina. Because the time window for SR regulation and D-serine alteration occurs after photoreceptor dysfunction in the AD retinas, it has limited value as a detection biomarker but may be useful as a topographic biomarker for staging severity and monitoring drug interventions in the eye or central nervous system.
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