Regenerative Therapy for Retinal Disorders

Journal of Ophthalmic & Vision Research | 2010 Oct | 5(4) | 250–264 | Narsis Daftarian, MD, Sahar Kiani, PhD, and Azadeh Zahabi, MS


Abstract

Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.


INTRODUCTION

Regenerative medicine intends to provide therapies for severe injuries or chronic diseases in which endogenous repair does not sufficiently restore the damaged tissue. These include congestive heart failure, osteoporosis, spinal cord injuries, Alzheimer’s and Parkinson‘s diseases, age-related macular degeneration, and retinitis pigmentosa.


Age-related macular degeneration (AMD) affects 10% to 20% of individuals over 65 years of age and is the leading cause of severe visual impairment in the elderly in industrialized nations. There are many senescent changes in the normal pigment epithelium including a decrease in retinal pigment epithelium (RPE) density, a clinically observed decrease in the pigmented appearance of RPE cells, and the accumulation of lipofuscin within RPE cells.2 In AMD, initial morphologic changes are associated with the formation of drusen and other deposits on Bruch’s membrane. Subsequently, RPE cell loss occurs, presumably via apoptosis associated with loss of cell attachment. Regenerative medicine aims to restore RPE cells before irreversible atrophy of foveal photoreceptors occurs.


Hereditary retinal degenerations are one of the major causes of blindness. This group of disorders includes retinitis pigmentosa (RP) which occurs at an incidence of 1 in 2000 individuals. The progressive loss of vision in RP is due to mutations in more than 100 identified genes which affect different cellular compartments in the photoreceptor cells (PRCs) or the underlying RPE. Treatment of these conditions and many other degenerative disorders is the goal of regenerative therapy.


STEM CELLS

Stem cells have attracted considerable attention, not only as a means of understanding metazoan development, but also as potential therapeutic agents for a spectrum of currently untreatable diseases. A stem cell is an unspecialized cell that can both self-renew (reproduce itself) and differentiate into functional phenotypes. Stem cells may originate from embryonic, fetal, or adult tissue and are broadly categorized accordingly. Embryonic stem cells (ESCs) are commonly derived from the inner cell mass of the blastocyst, an early (4 to 5 days) stage of the embryo. Embryonic germ cells (EGCs) are isolated from the gonadal ridge of a 5 to 10 week fetus. EGCs are derived from primordial germ cells, which ultimately give rise to eggs or sperms in the adult. Adult stem cells differ from ESCs and EGCs in that they are found in tissues after birth, and to date, have been found to differentiate into a narrower range of cell types, primarily demonstrating phenotypes of the originating tissue. Although the potential for self-renewal is a basic characteristic of these cells, but their ultimate differentiation into functional cells of the damaged organ, is more important. In other words, the main focus of regenerative research is on the optimal time for transplantation, in which the cells not only have the benefits of self-renewal, but also the best capacity to reach designated differentiation and bypass the untoward aspects of teratoma formation.


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