Retinal non-visual photoreception in space

Background: Circadian rhythm disruption occurs during spaceflight, leading to crew health and performance decrements. Spaceflight-related retinal changes, including oxidative stress and neuronal loss, have been previously reported in mice. Methods: Animal tissue from experiments aboard shuttle missions STS-133 (BALB/cJ mice, albino strain) and STS-135 (C57BL mice, pigmented strain), along with ground controls, was examined to determine survival of intrinsically photosensitive retinal ganglion cells (i_PRGC) and melanopsin expression in retinas of mice exposed to the spaceflight environment. Real-time _qPCR (RT_qPCT) and microarray approaches were used to analyze Opn4 (melanopsin) gene expression, while immunohistologic studies were conducted to detect melanopsin localization in the retina. Results: Opn4 expression was decreased in albino BALB/cJ mice exposed to spaceflight, as measured by RTqPCR, but not in C57BL mice samples as analyzed by microarray. Opn4 expression returned to control levels at 7 d postreturn in the BALB/cJ samples. Melanopsin positive RGCs were found in the expected proportion in all samples, except for the BALB/cJ samples at 1 d after flight, where virtually no immunoreactive cells were found. Discussion: Spaceflight environmental factors may affect the nonvisual function of the retina, mediated by a reduction in melanopsin expression and i_pRGC survival, contributing to circadian disruption.