A potential role for β‐ and γ‐crystallins in the vascular remodeling of the eye

Zhang, Cheng; Gehlbach, Peter; Gongora, Céline; Cano, Marisol; Fariss, Robert N.; Hose, Stacey; Nath, Avindra; Green, William R.; Goldberg, Morton F.; Zigler, J. Samuel; Sinha, Debasish

doi:10.1002/dvdy.20494

Cited by 46 publications

(49 citation statements)

References 59 publications

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“…Remodeling is critical to retinal development and maturation, by generating the different cell types in proper ratios and positions, which then migrate to correct layers before finally forming synaptic connections. Third, we have recently shown persistence of the fetal vasculature in this model (Zhang et al, 2005). Regression of the fetal vasculature is an essential element of eye development, apoptosis is vital to this process (Lobov et al, 2005).…”

Section: Maumenee Personal Communication)mentioning

confidence: 75%

“…Our previous study demonstrated expression of βA3/A1-crystallin mRNA in the retina (Zhang et al, 2005). To determine its cellular localization within the retina, laser-capture microdissection was employed.…”

Section: Maumenee Personal Communication)mentioning

confidence: 99%

“…We previously described a naturally occurring mutation (Nuc1) in the Sprague-Dawley rat with a novel and unusual eye phenotype Hose et al, 2005;Zhang et al, 2005;Gehlbach et al, 2006). Nuc1 is inherited as a single Mendelian locus with viable homozygotes and an intermediate phenotype in heterozygotes.…”

Section: Introductionmentioning

confidence: 99%

“…Mutations in βA3/A1-crystallin are well known to cause cataract in both humans and mice (Kannabiran et al, 1998;Bateman et al, 2000;Qi et al, 2004;Ferrini et al, 2004;Reddy et al, 2004;Graw et al, 1999). In Nuc1 homozygotes, however, in addition to cataracts, severe retinal and other ocular abnormalities are apparent Hose et al, 2005;Zhang et al, 2005;Gehlbach et al, 2006). These rats manifest persistence of the fetal intraocular vessels even after development of the retinal vessels.…”

Section: Introductionmentioning

confidence: 99%

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βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Sinha

Klise

Sergeev

et al. 2008

Molecular and Cellular Neuroscience

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Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague-Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the βA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina.

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Section: Maumenee Personal Communication)mentioning

confidence: 75%

Section: Maumenee Personal Communication)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Sinha

Klise

Sergeev

et al. 2008

Molecular and Cellular Neuroscience

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“…␣-Crystallins belong to the small heat shock protein family and prevent aberrant protein interactions and/or degradation and regulate apoptosis (13)(14)(15)(16). The functions of the ␥-and ␤-crystallins are less clear, although like the ␣ family they are involved in chaperone activity, apoptosis regulation, and vascular remodeling in the retina (17,18).…”

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confidence: 99%

The Retinal Proteome in Experimental Diabetic Retinopathy

Fort

Freeman

Losiewicz

et al. 2009

Molecular & Cellular Proteomics

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Diabetic retinopathy is the leading cause of blindness in working age persons. Targeted studies have uncovered several components of the pathophysiology of the disease without unveiling the basic mechanisms. This study describes the use of complementary proteomic and genomic discovery methods that revealed that the proteins of the crystallin superfamily are increased dramatically in early diabetic retinopathy. Orthogonal methods confirmed that the amplitude of the up-regulation is greater than other changes described so far in diabetic retinopathy. A detailed time course study during diabetes showed differential up-regulation of the different isoforms of the crystallins superfamily. ␣-and ␤-crystallins were regulated primarily at the translation level, whereas ␥-crystallins were also regulated transcriptionally. We also demonstrated cell-specific patterns of expression of the different crystallins in normal and diabetic rat retinas. Diabetic retinopathy is the leading cause of blindness in working age persons, and despite numerous studies, the pathophysiological mechanisms, especially during the early stages of diabetes, remain to be elucidated. Diabetic retinopathy develops, to some degree, in nearly all patients with diabetes and is the most common cause of new cases of blindness among adults. The predominant causes of vision loss are clinically significant macular edema and proliferative diabetic retinopathy, but vision impairment can be prevented or minimized if the retinopathy is identified in its early stages. Diabetic retinopathy includes microvascular and neuronal, glial, and microglial cell defects early in the course of the disease before clinically visible vascular lesions. Photoreceptor and ganglion cell death occurs as early as 2-4 weeks after the onset of diabetes (1-3).Because of the difficulty of studying the mechanisms of the early stages of diabetes in humans, rodent models of type 1 and type 2 diabetes have been developed. Those models have been used to study various specific aspects of early stages of diabetic retinopathy including blood retinal barrier leakage (4), growth factor signaling such as the insulin/insulinlike growth factor receptor and vascular endothelial cell receptor pathways (5, 6), and oxidative stress mechanisms such as reactive oxygen species and advanced glycation end product production (7,8). These targeted studies provide valuable information on different aspects of the pathology and are useful in new therapeutic development, but more detailed discovery research is also needed to understand the full range of metabolic dysregulation that leads to diabetes complications. Proteome profiling using two-dimensional (2D) 1 DIGE and/or isobaric tag for relative and absolute quantitation (iTRAQ) are methods that can characterize new pathophysiological components and potential therapeutic targets.Several studies have used 2D DIGE to gain a better understanding of diabetic complications in the heart and retina (9 -12). These global approaches revealed biochemical changes in the ret...

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Diseases of protein aggregation and the hunt for potential pharmacological agents

Wang

Yamamoto

et al. 2008

Biotechnology Journal

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Protein aggregation is a ubiquitous phenomenon significant to all aspects of science. Notably, the formation of protein aggregates is frequently encountered in biochemical research and biopharmaceutical industry. Formation of protein aggregates is generally regarded to be associated with partially folded intermediate species that are susceptible to self-association due to the exposure of hydrophobic core. Evidence supports the concept that the formation of aggregates in vitro is a generic property of proteins. In human etiology, more than 20 different devastating human diseases have been reported to be associated with protein aggregation. Although protein aggregation diseases have been the center of intense research, much remains to be learned regarding the underlying molecular mechanisms. In this review, the general background information on protein aggregation is first provided. Next, we summarize the properties, characteristics and causes of protein aggregates. Finally, from the perspectives of epidemiology, pathogenesis, existing mechanisms, relevant hypotheses, and current as well as potential therapeutic approaches, two examples of protein aggregation diseases, Alzheimer's disease and cataract, are briefly discussed. Importantly, while a variety of molecules have been suggested, the effective therapeutic drugs for curing the diseases involving protein aggregation have yet to be identified. We believe that a better understanding of the mechanisms of protein aggregation process and an extensive investigation into the drug penetration, efficacy, and side effects will certainly aid in developing the successful pharmacological agents for these diseases.

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A potential role for β‐ and γ‐crystallins in the vascular remodeling of the eye

Cited by 46 publications

References 59 publications

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

The Retinal Proteome in Experimental Diabetic Retinopathy

Diseases of protein aggregation and the hunt for potential pharmacological agents

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