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- retinal progenitor cells
- retinal progenitor cells
- age related macular degeneration
- retinal dystrophies
- retinal pigment epithelium
It has been generally assumed that the adult mammalian eye is devoid of retinal stem cells or progenitor cells as self renewing and multipotential cells. In a previous study, however, identification of retinal stem cells in the mouse eye has been reported, representing a possible substrate for retinal regeneration.1 It has been paralleled by other studies on multipotent precursor cells in the ciliary margin of the frog retina,2 the role of Muller glia for neural regeneration in the postnatal chicken retina,3 progenitor cell proliferation and horizontal cell genesis in the mammalian retina,4 and differentiation of human neural stem cells into retinal cells.5 The retinal progenitor or stem cells were thought to be located in the region of the ciliary body.1 Examining rhesus monkey eyes, it was the purpose of the present histological study to look for a region in the monkey pars plana area which could serve as nidus of retinal stem cells.
The study included 11 normal eyes of rhesus monkeys with a mean age of 18.2 (SD 2.8) years. The eyes had been enucleated, fixed in formaline, and prepared for light microscopy. An anterior-posterior segment going through the pupil and the optic nerve was cut out of the fixed globes. The segments were dehydrated in alcohol, embedded in paraffin, sectioned for light microscopy, and stained by haematoxylin eosin or by the periodic acid Schiff (PAS) method. Using light microscopy, different regions of the peripheral retina and of the pars plana region of the ciliary body were examined for regularity, cell size, and nucleus size. The study design complied with the National Institute of Health’s guidelines as well as the University of Iowa Institutional Guidelines for the Care and Use of Laboratory Animals, and the guidelines of ARVO.
In all eyes examined, the inner non-pigmented layer of the posterior pars plana region of the ciliary body close to the ora serrata was multilayered. The cells were irregular in size and shape (fig 1). There was a continuous transition to the more anteriorly located region of the pars plana in which the inner non-pigmented layer was monolayered and regularly arranged. Here, the cell shape was columnar, and the cell nuclei were located in the basal cell region (fig 2). In the pars plicata of the ciliary body, the inner non-pigmented layer was monolayered with a cuboidal cell shape and the cell nuclei located in the basal region of the cell (fig 3). In contrast to the monkey eyes, in a human globe, the inner non-pigmented layer in the posterior pars plana region was monolayered and more regularly arranged (fig 4).
In rhesus monkeys close to the ora serrata in the posterior part of the pars plana region, the inner non-pigmented pars plana epithelium is multilayered and irregularly structured showing nuclei of varying shape and location within the cell body. This heterogeneous morphology differs from the regular anatomy of the inner non-pigmented layer of the anterior region of the pars plana or the inner non-pigmented layer of the pars plicata. It is in contrast to anatomic textbooks generally describing the inner layer of the posterior pars plana as monolayered and regularly structured.6 It may correspond with the retina of fish and amphibians in which the continuous growth of the retina throughout life is accomplished by new retinal cells which are continually added at the anterior margin of the retina in a circumferential zone of cells, also known as the ciliary marginal zone.7,8 Correspondingly, it has recently been reported that new neurons are added to the retina of the chicken via proliferation and subsequent differentiation of neurons and glia at the retinal margin in a zone which is highly reminiscent of the ciliary marginal zone of lower vertebrates.9 Other investigations revealed that putative retinal stem cells could be isolated from the ciliary margin of the adult mouse.1 Recently, Kubota and colleagues investigated the eyes of an avian species, the quail, a marsupial species, the opossum, and a mammal species, the mouse.10 They found that the ciliary marginal zone cells gradually diminished during the vertebrate evolution. It corresponds with the present study, in which the inner non-pigmented layer in the posterior part of the pars plana region in a human globe was monolayered (fig 4) and appeared to be more regularly structured than in the monkeys eyes (fig 1–3).
Future studies may reveal whether cells originating from the irregularly structured inner non-pigmented layer of the posterior region of the pars plana close to the ora serrata may show characteristics of retinal progenitor cells, and whether they may be suitable for harvesting and cultivation to obtain autologous retinal progenitor cells for subfoveal transplantation in patients with degenerative or dystrophic diseases of the retina and retinal pigment epithelium, such as non-exudative age related macular degeneration.
Supported by grant EY-1576 from the US National Institutes of Health, in part by unrestricted grants from Research to Prevent Blindness, Inc, New York, USA. Dr S S Hayreh is a Research to Prevent Blindness Senior Scientific Investigator.
Proprietary interest: none.
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