Transplantation of Retinal Pigment Epithelial, Photoreceptor and other Cells as Treatment for Retinal Degeneration

Litchfield, T.M.; Whiteley, Simon J.O.; Lund, Raymond D.

doi:10.1006/exer.1996.0253

Cited by 36 publications

(15 citation statements)

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“…The first includes attempts at replacing defective genes (43)(44)(45)(46), the second includes attempts at slowing photoreceptor cell loss by using growth factors (37,42) or protecting putatively remaining cones with vitamin supplements (47), and the third includes attempts at slowing such cell loss by grafting different retinal cell populations (48,49). Recently, evidence has been provided using the same rd mouse model that early in vivo gene transfer produces a significant delay in photoreceptor cell death (46).…”

Section: Discussionmentioning

confidence: 99%

Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse

Mohand‐Saïd¹,

Deudon-Combe²,

Hicks³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

185

123

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The role of cellular interactions in the mechanism of secondary cone photoreceptor degeneration in inherited retinal degenerations in which the mutation specifically affects rod photoreceptors was studied. We developed an organ culture model of whole retinas from 5-week-old mice carrying the retinal degeneration mutation, which at this age contain few remaining rods and numerous surviving cones cocultured with primary cultures of mixed cells from postnatal day 8 normal-sighted mice (C57BL͞6) retinas or retinal explants from normal (C57BL͞6) or dystrophic (C3H͞He) 5-week-old mice. After 7 days, the numbers of residual cone photoreceptors were quantified after specific peanut lectin or anti-arrestin antibody labeling by using an unbiased stereological approach. Examination of organ cultured retinas revealed significantly greater numbers of surviving cones (15-20%) if cultured in the presence of retinas containing normal rods as compared with controls or cocultures with rod-deprived retinas. These data indicate the existence of a diffusible trophic factor released from retinas containing rod cells and acting on retinas in which only cones are present. Because cones are responsible for high acuity and color vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to define interactions between retinal photoreceptor types.Despite recent advances, our understanding of the mechanisms underlying visual malfunction and cell loss in retinitis pigmentosa (RP) has provided few clinically significant clues to improve retinal cell survival (1-3). RP forms a group of inherited photoreceptor dystrophies characterized largely by early features of rod photoreceptor impairment (1, 4). Most identified forms of RP are caused by defects in proteins restricted to rod photoreceptors (5-8). Yet, at various stages of the disease, a loss of the photopic function reflecting degeneration of cone photoreceptors is found consistently (1, 4). Of extreme importance for the patient, cone cell death and its functional consequences appear to be secondary events. No current data exist to account for cone cell death, but observations made on animal models of RP provide arguments for cone survival depending on the presence of rods. In several models with selective elimination of rods, secondary loss of cones is observed (9-11). The cause of rod cell death in these animals, either transgenic or spontaneous mutants, cannot account for direct cone cell loss (9-17). Putative mechanisms of cone cell death include the liberation of endotoxins by degenerating rods, environmental alteration, or deprivation of rod-derived trophic factor(s). Recent studies using chimeras of normal and transgenic mice carrying mutations in rods showed that photoreceptor cell death was diffuse rather than restricted to areas with mutations in rods, providing evidence for a role of cellular interactions between photoreceptors in survival and degeneration of these cells (18). Based on these dat...

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Section: Discussionmentioning

confidence: 99%

Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse

Mohand‐Saïd¹,

Deudon-Combe²,

Hicks³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

185

123

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“…This baseline is also critical for measuring the success of treatments for such defects, such as retinal transplantation (Litchfield et al 1997;Radner et al 2001Radner et al , 2002, regeneration (Porciatti et al 1996;Travis et al 1992), or prostheses (Humayun 2001;Margalit et al 2002), which aim to duplicate normal visual responses. By defining cell classes as clusters in an easy-to-measure parameter space, we provide an objective description of what normal visual responses are, which can be retraced exactly by other investigators.…”

Section: Importance Of Cell Classificationmentioning

confidence: 99%

Classification of Retinal Ganglion Cells: A Statistical Approach

Carcieri

Jacobs

Nirenberg

2003

Journal of Neurophysiology

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Carcieri, Stephen M., Adam L. Jacobs, and Sheila Nirenberg. Classification of retinal ganglion cells: a statistical approach. J Neurophysiol 90: 1704 -1713, 2003; 10.1152/jn.00127.2003. Numerous studies have shown that retinal ganglion cells exhibit an array of responses to visual stimuli. This has led to the idea that these cells can be sorted into distinct physiological classes, such as linear versus nonlinear or ON versus OFF. Although many classification schemes are widely accepted, few studies have provided statistical support to favor one scheme over another. Here we test whether some of the most widely used classification schemes can be statistically verified, using the mouse retina as the model system. We used a cluster analysis approach and focused on 4 standard response parameters: 1) response latency, 2) response duration, 3) relative amplitude of the ON and OFF responses, and 4) degree of nonlinearity in the stimulus-to-response transformation. For each parameter, we plotted its distribution and tested quantitatively, using a bootstrap method, whether it divided into distinct clusters. Our analysis showed that mouse ganglion cells clustered into several groups based on response latency, duration, and relative amplitude of the ON and OFF responses, but did not cluster into more than one group based on degree of nonlinearity-the latter formed a single, large, continuous group. Thus while some well-known schemes for classifying ganglion cells could be statistically verified, others could not. Knowledge of which schemes can be confirmed is important for building models of how retinal output is processed and how retinal circuits are built. Finally, this cluster analysis approach is general and can be used to test other classification proposals as well, both physiological and anatomical.

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“…In the past 20 years, retinal transplantation has been investigated. Various dissociated cells and tissue microaggregates were transplanted via subretinal and intravitreal injection and showed disorganized or incorrectly localized grafts [26][27][28][29]. Studies of retinal pigment epithelial (RPE) cells showed the importance of cellular continuity and polarity in the success of transplantation [30][31][32].…”

Section: Polymer Scaffoldsmentioning

confidence: 99%

Synthetic Polymer Scaffolds for Stem Cell Transplantation in Retinal Tissue Engineering

2011

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Age-related macular degeneration and retinitis pigmentosa are two leading causes of irreversible blindness characterized by photoreceptor loss. Cell transplantation may be one of the most promising approaches of retinal repair. However, several problems hinder the success of retinal regeneration, including cell delivery and survival, limited cell integration and incomplete cell differentiation. Recent studies show that polymer scaffolds can address these three problems. This article reviews the current literature on synthetic polymer scaffolds used for stem cell transplantation, especially retinal progenitor cells. The advantages and disadvantages of different polymer scaffolds, the role of different surface modifications on cell attachment and differentiation, and controlled drug delivery are discussed. The development of material and surface modification techniques is vital in making cell transplantation a clinical success.

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Transplantation of Retinal Pigment Epithelial, Photoreceptor and other Cells as Treatment for Retinal Degeneration

Cited by 36 publications

References 0 publications

Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse

Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse

Classification of Retinal Ganglion Cells: A Statistical Approach

Synthetic Polymer Scaffolds for Stem Cell Transplantation in Retinal Tissue Engineering

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