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.
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 Müller cell cultures was investigated.
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.
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 Aβ nor 17β-estradiol increased SR, but the combination of both did in Müller cell cultures. In contrast, 17β-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.