Abstract
Purpose :
The C57BL/6-RPGRtm1Sti mouse model for X-linked retinitis pigmentosa (XLRP model) carries a point mutation in the mutational hotspot exon ORF15 of the rpgr gene. To assess the reduction of photoreceptor connecting cilium (cc) length in the XLRP mouse model, immunohistochmically labeled cc were evaluated and compared to cc length in wildtype mice. Our central question was whether there is an age related reduction of cc length in photoreceptors (PRs) of the XLRP mouse model vs healthy wild type cc.
Methods :
Hemizygous male or homozygous female mice (age: 3, 9 or 15 months) of the XLRP model and C57BL/6J wild type mice with respective age were sacrificed, enucleated and the eyes immediately frozen in embedding medium to cut frozen sections. Connecting cilium region was analyzed after immunohistochemical labeling with antibodies against Centrin, AcTub and RPGR using confocal laser scanning microscopy.
Results :
Only Centrin and AcTub antibodies labeled the cc region of PRs in both mouse lines completely, in contrast to the RPGR antibody. Within each mouse line, the cc length got shorter with age. In XLRP mice, cc length is significantly shorter at 3 and 9 months compared to wild type retina. At 15 months, cc length in PRs of both mouse lines show no significant difference.
Conclusions :
During the course of life cc length of PRs is decreasing significantly in both mouse lines investigated. In 3-months old XLRP mice, the cc length corresponds to 9-months old wild type mice. Therefore, age correlated reduction of photoreceptor cc length starts earlier in XLRP mouse model compared to wild type mice.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.