Use of Iris Pigment Epithelium to Replace Retinal Pigment Epithelium in Age-Related Macular Degeneration

Cai, Hui; Shin, Min Cheol; Tezel, Tongalp H.; Kaplan, Henry J.; Priore, Lucian V. Del

doi:10.1001/archopht.124.9.1276

Cited by 27 publications

(17 citation statements)

References 88 publications

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“…Retinal aging is also associated with changes in expression of genes involved in the complement cascade; the relationship of altered expression of these genes to the development of age-related diseases such as AMD remains to be elucidated. Any individual change or combination of changes may be responsible for altering retinal gene expression (Cai et al, 2006; Han et al, 2007). …”

Section: Discussionmentioning

confidence: 99%

Effects of Aging and Anatomic Location on Gene Expression in Human Retina

Cai¹,

Fields²,

Hoshino³

et al. 2012

Front. Ag. Neurosci

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Objective: To determine the effects of age and topographic location on gene expression in human neural retina. Methods: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. Results: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young, or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10, and SFRP2) which are preferably expressed in the periphery. Conclusion: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases.

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Section: Discussionmentioning

confidence: 99%

Effects of Aging and Anatomic Location on Gene Expression in Human Retina

Cai¹,

Fields²,

Hoshino³

et al. 2012

Front. Ag. Neurosci

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“…3H). We also examined the transcriptional levels of genes critical to RPE functions, such as those implicated in mediating cell junction to nuclear signaling (␤-catenin) (72), extracellular matrix remodeling and/or adhesion (collagen VI ␣1/3, versican) (73,74), inflammation and cytokine signaling (Stat3, Stat5, and CXCR4 (CXC chemokine receptor type 4 (fusin/ CD184)) (64,75,76), receptor tyrosine kinase signaling (ErbB1/2) (22, 77), and markers of RPE (cytokeratin 18, miR-224, and miR200b) (78). We found that RPE of RPE-cre::Ranbp2 Ϫ/Ϫ mice exhibit strong deregulation of the transcriptional expression of all these genes at P14 (Fig.…”

Section: Cd11bmentioning

confidence: 99%

Selective Impairment of a Subset of Ran-GTP-binding Domains of Ran-binding Protein 2 (Ranbp2) Suffices to Recapitulate the Degeneration of the Retinal Pigment Epithelium (RPE) Triggered by Ranbp2 Ablation

Patil

Saha

Senda

et al. 2014

Journal of Biological Chemistry

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Background: Ranbp2 and its Ran-GTP-binding domains' roles in RPE survival/function, a multidisease target, are elusive. Results: RPE undergoes degeneration, disruptions of proteostasis of Ranbp2 partners, and blood-retinal barrier upon Ranbp2 ablation. Impairment of selective Ran-GTP-binding domains of Ranbp2 suffices to promote RPE degeneration. Conclusion: Ran GTPase regulation by Ranbp2 is vital to RPE. Significance: Ranbp2-dependent targets/mechanisms with therapeutic potential in RPE degeneration are uncovered. The retinal pigment epithelium (RPE) 6 is a critical component of the blood-retinal barrier and maintains retinal homeostasis by filtering damaging light, nourishing the neural retina, replenishing the 11-cis-retinal chromophore to photoreceptors, and phagocytizing damaged (photo-oxidized) outer segments of photoreceptors (1-3). RPE dysfunction underlies disparate diseases promoting RPE degeneration, such as atrophic and neovascular age-related macular degeneration (4 -6), * This work was supported, in whole or in part, by National Institutes of Health Grants EY019492, GM083165, and GM083165-04S1 (to P. A. F.), 2P30-EY005722 (to the Duke University Eye Center), and 5P30NS061789 (to the Duke Neurotransgenic Laboratory). This work was also supported by the Foundation Fighting Blindness bestrophinopathies (7), and various forms of retinal dystrophies (e.g. retinitis pigmentosa, Leber congenital amaurosis) (8 -12). The cause-effect mechanisms of RPE degeneration are not understood, but they appear to arise from the interplay of multifactorial events impinging on heterogeneous genetic predispositions, noxious insults, and senescence that culminate with cytotoxicity to the RPE (13-21). Retinal pigment epithelium (RPE) degeneration underpins diseases triggered by disparate genetic lesions, noxious insultsEmerging studies indicate that the modular and pleiotropic Ranbp2 (Ran (Ras-related nuclear protein)-binding protein 2) plays critical and cell type-dependent roles in cell survival, proliferation, or functions upon intrinsic or extrinsic pathological stressors. For example, haploinsufficiency of Ranbp2 in an inbred genetic background confers neuroprotection to photoreceptor degeneration upon photo-oxidative stress and modulates glucose tolerance (22-24), whereas it increases the susceptibility of mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-elicited Parkinsonism (25) or carcinogenesis (26). Interestingly, RANBP2 is also a substrate for degradation by PARKIN (27,28), whose impairment causes familial and sporadic Parkinson (29 -31) or multisite oncogenesis (32,33). Further, Ranbp2 loss in cones photoreceptors also elicits non-autonomous death of healthy rod photoreceptors (34), whereas asymptomatic mutations in human RANBP2 predispose the basal ganglia to acute necrotic damage (e.g. encephalopathy) upon exposure to various infectious agents (35-37). A parsimonious model of the multifold activities of multimodular Ranbp2 arises from structure-function analyses of Ranbp2, whereby the dynamic recruitme...

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“…[60] However, the procedure of obtaining IPE cells itself was considered to be complicated, and the IPE cells in vitro , although capable of phagocytosis of rod photoreceptor outer segment, is considered to lack enzymes involved in retinoid visual cycle. [61] Both fetal RPE and IPE do not have the ideal characteristics of cells for RPE replacement strategy. Recently, pluripotent stem cells' source such as human embryonic stem cell (hESC) has been shown to be a renewable source or functional RPE cells.…”

Section: Source Of Functional Cells During Cell Replacement Therapiesmentioning

confidence: 99%

Pluripotent stem cells: A therapeutic source for age-related macular degeneration

Parameswaran

Krishnakumar

2017

Indian J Ophthalmol

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Age-related macular degeneration (AMD) leads to progressive loss of central vision in the elderly. At a cellular level, there is aging of the retinal pigment epithelial (RPE) cells, and accumulation of lipofuscin that interferes with the proper functioning of RPE which eventually leads to apoptosis. Treatment depends on the stage of the disease. Wet AMD which has neovascularization is managed by local therapies such as laser photocoagulation and photodynamic therapy and is managed with injections of antivascular endothelial growth factor-based therapy. Unlike the wet AMD, an effective therapy does not exist for dry AMD and geographic atrophy. Cell replacement therapy has shown promise. This review discusses the opportunities in the various types of cell-based therapy, their limitations, and what is possible for India.

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Use of Iris Pigment Epithelium to Replace Retinal Pigment Epithelium in Age-Related Macular Degeneration

Cited by 27 publications

References 88 publications

Effects of Aging and Anatomic Location on Gene Expression in Human Retina

Effects of Aging and Anatomic Location on Gene Expression in Human Retina

Selective Impairment of a Subset of Ran-GTP-binding Domains of Ran-binding Protein 2 (Ranbp2) Suffices to Recapitulate the Degeneration of the Retinal Pigment Epithelium (RPE) Triggered by Ranbp2 Ablation

Pluripotent stem cells: A therapeutic source for age-related macular degeneration

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