Gradual morphogenesis of retinal neurons in the peripheral retinal margin of adult monkeys and humans

Abstract

The adult mammalian retina has for long been considered to lack a neurogenerative capacity. However, retinal stem/progenitor cells, which can originate retinal neurons in vitro, have been recently reported in the ciliary body of adult mammals. Here we explored the possibility of retinal neurogenesis occurring in vivo in adult monkeys and humans. We found the presence of cells expressing molecular markers of neural and retinal progenitors in the nonlaminated retinal margin and ciliary body pars plana of mature primates. By means of immunohistochemistry and electron microscopy we also observed photoreceptors and other retinal cell types in different stages of morphological differentiation along the peripheral retinal margin. These findings allow us to extend to primates the idea of neurogenesis aimed at retinal cell turnover throughout life. J. Comp. Neurol. 511:557–580, 2008. © 2008 Wiley‐Liss, Inc.

Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue

“…2b). When hESCderived retinal epithelium was treated with CHIR99021 and SU5402 (days [18][19][20][21][22][23][24] and subsequently cultured in NRdifferentiation medium (not containing these inhibitors) from day 24 (Fig. 2a, condition 3), the majority of epithelium (in B70% of aggregates) repressed Mitf expression in their major portions, regained Chx10 expression and increased the epithelial thickness ( Fig.…”

“…The mammalian foetal eye also contains a peripheral NR zone resembling the chick embryonic CM in molecular marker expression, and this zone contains a substantial number of stem cells 10,14,15 (Hereafter, these cells are referred to as 'CM stem cells'). The presence of a small number of retinal stem cells at the ciliary region in the adult mammalian eye has also been reported [16][17][18][19][20] , although the extent of their in vivo contribution to the maintenance and regeneration of adult retinal tissue remains elusive.…”

Neuropeptide Y system in the retina: From localization to function

“…Several studies have shown that fish, amphibians, birds, rodents and humans present neural progenitors in the their adult eyes with capacity to generate all retinal cell types (Ahmad, 2001 ; Cepko 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Coles et al, 2004;Johns, 1977;Martinez-Navarrete et al, 2008;Reh and Fischer, 2001;Straznicky and Gaze, 1971;Tropepe et al, 2000;Xu et al, 2007). The identification, characterization, and even transplantation of neural progenitor stem cells in the eye may open new opportunities for the treatment of several ocular diseases characterized by retinal cell death, such as retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and glaucoma (Ahmad, 2001;Bernardos et al, 2007;Ohta et al, 2008;Ooto et al, 2004;Tropepe et al, 2000).…”

Partial Rescue of Retinal Function in Chronically Hypoglycemic Mice

“…Such changes in connectivity, also known as remodeling, are a common event in degenerations caused by defects in the sensory retina and is generally associated with photoreceptor death (see reviews by Marc et al 27 and Jones and Marc 28 ). Cone death, 29,30 rod death, 22,24,[31][32][33][34][35] and lack of rods during development 36 are associated with cellular remodeling and ectopic synaptogenesis. Cellular remodeling can also result from aging, 37,38 light damage, 39 and detachment and reattachment of the RPE.…”