Animal models of oxygen-induced retinopathy

Madan, Ashima; Penn, John S.

doi:10.2741/1056

Cited by 92 publications

(24 citation statements)

References 65 publications

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“…Thus, the current animal models of DR are not considered fully reflective of human DR (93). Investigators have turned their attention to non-diabetic models of retinal neovascularization caused by branch vein occlusion, oxygen-induced retinopathy (94), or overexpression of growth factors such as VEGF (95) or IGF-1 (96). Most studies investigating cell effects of DR have involved EPC and those patients with earlier stages of disease (NPDR) exhibit reduced number of EPC compared to higher levels in patients with PDR (97, 98), most probably due to inflammatory reactions in damaged tissue and increased mobilization of EPC from the bone marrow in later stages of disease.…”

Section: Msc-based Therapies For Diabetic Microvascular Complicationsmentioning

confidence: 99%

Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

et al. 2014

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The worldwide increase in the prevalence of Diabetes mellitus (DM) has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency but also due to their paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. This review focuses on the potential use of MSCs as a regenerative medicine in microvascular and secondary complications of DM and will discuss the challenges and future prospects of MSCs as a regenerative therapy in this field. MSCs are believed to have an important role in tissue repair. Evidence in recent years has demonstrated that MSCs have potent immunomodulatory functions resulting in active suppression of various components of the host immune response. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. Through a combination of the above characteristics, MSCs have been shown to exert beneficial effects in pre-clinical models of diabetic complications prompting initial clinical studies in diabetic wound healing and nephropathy. Challenges that remain in the clinical translation of MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery, homing of these cells to tissues of interest with high efficiency, clinically meaningful engraftment, and challenges with cell manufacture. An issue of added importance is whether an autologous or allogeneic approach will be used. In summary, MSC administration has significant potential in the treatment of diabetic microvascular and secondary complications but challenges remain in terms of engraftment, persistence, tissue targeting, and cell manufacture

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Section: Msc-based Therapies For Diabetic Microvascular Complicationsmentioning

confidence: 99%

Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

et al. 2014

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“…This relative hyperoxia is exacerbated by supplemental oxygen. 17 In response to the elevated levels of oxygen, expression of hypoxia-driven angiogenic factors is downregulated, vessel growth ceases, and already formed vessels constrict and retract. 9,16 …”

Section: Pathogenesis Of Ropmentioning

confidence: 99%

“…17 The mouse model of oxygen-induced retinopathy (OIR) has become the most commonly used model for investigations into the molecular pathogenesis of ROP as the model offers reproducibility of the phenotype, a reliable method of quantifying retinal neovascularization, and the ease of genetic manipulation. 18 The degree of vascular development in the retina of the neonatal mouse most closely approximates the retina of a premature infant at 5 months GA.…”

Section: Pathogenesis Of Ropmentioning

confidence: 99%

Retinopathy of Prematurity: Current Concepts in Molecular Pathogenesis

Heidary

VanderVeen

Smith

2009

Seminars in Ophthalmology

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Retinopathy of prematurity is marked by the proliferative vascularization of the retina in preterm babies. An understanding of the molecular pathogenesis of ROP provides the basis for identifying novel therapeutic targets for treatment. Using the mouse model of oxygen-induced retinopathy, the roles of the hypoxia induced factors vascular endothelial growth factor and erythropoietin as well as the maternally derived factors insulin-like growth factor-1 and omega-3 polyunsaturated fatty acids have begun to be elucidated. Understanding the phase specific effects of these factors will serve to guide the development of non destructive treatments for ROP and for other ischemic retinopathies including diabetic retinopathy and neovascular age-related macular degeneration.

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“…Furthermore, by electron microscopy, the outer and inner segments of the ROP rods were disorganized and dysmorphic (Fulton et al, 1999b). Thus, the ROP rats had functional and structural evidence of hypoxic and hyperoxic injury induced by ambient conditions (Barnett et al, 2010; Dodge et al, 1996; Liu et al, 2006a; Madan and Penn, 2003; Penn et al, 1994; Reynaud et al, 1995; Roberto et al, 1996; Shao et al, 2011). It has since been confirmed that both hypoxia and hyperoxia are injurious to the immature rods (Wellard et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The neural retina in retinopathy of prematurity

Hansen

Moskowitz

Akula

et al. 2017

Progress in Retinal and Eye Research

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Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP.

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Animal models of oxygen-induced retinopathy

Cited by 92 publications

References 65 publications

Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

Retinopathy of Prematurity: Current Concepts in Molecular Pathogenesis

The neural retina in retinopathy of prematurity

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