Three independent images randomly obtained from the same eye were analyzed to calculate the proportion of recoverin-positive cells that were also positive for rhodopsin (Rho) or PNA (PNA) or neither (Rcv) per animal. of acquired retinal degeneration in adult wild-type mice (P30) increased the number of BrdU-positve cells by roughly fourfold and recoverin-positive cells by approximately 17-fold in the pars plana. Moreover, some (approximately 1.5%) of the recoverin-positive cells were newly generated from dividing retinal progenitors in the adult pars plana. Conclusions In response to retinal damage, an increased number of immature retinal neurons/retinal precursors was observed in the pars plana of mice with acquired and inherited retinal UBCS039 degeneration. Some of these cells differentiated from proliferating cells even after retinal histogenesis. Introduction In fishes and amphibians, a circumferential zone in the retinal margin, called the ciliary marginal zone (CMZ), produces all types of retinal neurons, and thereby continuously regenerates the retina throughout life [1-3]. While the CMZ increases its production of new neurons in response to retinal injury, neurogenesis by the intrinsic stem cells within the mature retina in fishes or neural transdifferentiation of the retinal pigment epithelium in most amphibians can also UBCS039 take place to promote the regeneration of the retina [1-3]. However, in mammals, despite the recognition of adult germinal zones for neural regeneration of areas in the central nervous system [4,5], such as the subgranular zone for the olfactory bulb [6,7] and the utricular sensory epithelium for the inner hearing [8], a zone for retinal regeneration capable of replacing lost neurons has not been defined. There is evidence suggesting the adult ciliary epithelium consists of stem cells that have the potential to proliferate and communicate markers specific to retinal neurons in mammals [9-14], including humans [15]. However, the in situ distributions or tasks of these cells are still unclear. Recently, we found that the neuroblast coating, a retinal coating composed of retinal progenitor cells seen only during retinal development, extended into the ciliary epithelium of the pars plana during ocular development in wild-type mice [16]. In addition, many cone and pole photoreceptor precursors (termed immature photoreceptors/photoreceptor precursors in the current study) in various phases of morphological differentiation were recognized in the pars plana UBCS039 during retinal histogenesis. However, once the gross development of the retina was total, such precursors were rare in the ciliary epithelium. Nonetheless, these observations suggested the ciliary epithelium of the pars plana may play an important part in the generation of retinal neurons. In the brain, it is well known that neural stem cells proliferate in response to neural damage Rabbit Polyclonal to OR5A2 actually in adult mammals [17-19]. Consistent with these reports, we have also reported an increased quantity of cells immunopositive UBCS039 for any retinal marker in the adult pars plana after toxin-induced retinal degeneration [16]. However, it is not known whether these cells were generated from dividing cells or differentiated from post-mitotic cells. In this study, we examined two mouse models with retinal degeneration, inherited and acquired, and found that a small fraction of immature retinal neurons/retinal precursors was newly generated from dividing cells after retinal histogenesis. Methods Animals All experimental methods were performed in accordance with the guidelines of the Institute for Laboratory Animal Study (Guidebook for UBCS039 the Care and Use of Laboratory Animals) and Nagoya University or college School of Medicine for the use of animals. C57BL/6J mice were used as wild-type settings and for the N-methyl-N-nitrosourea (MNU; Clea, Tokyo, Japan) injection study. C3H/HeJ mice (mice; Clea, Tokyo, Japan) were used like a murine model of inherited retinal degeneration [20]. All mice were fed on a basal diet (CE-2; Clea, Tokyo, Japan) and water. They were kept on a 12-h light-dark cycle in a standard cage placed in a temp- and humidity-controlled environment. The number of mice used in each quantitative experiment is definitely indicated in Table 1. A.

Three independent images randomly obtained from the same eye were analyzed to calculate the proportion of recoverin-positive cells that were also positive for rhodopsin (Rho) or PNA (PNA) or neither (Rcv) per animal