The Structure Of Posterior Subcapsular Cataracts In The Royal College Of Surgeons (RCS) Rats

Al-Ghoul, K. J.; Novak, L.A.; Kuszak, J.R.

doi:10.1006/exer.1998.0505

Cited by 32 publications

(17 citation statements)

References 20 publications

(19 reference statements)

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“…Because the suture line patterns represent precise migratory elongation and destination of fiber cells in the lens, any defects in elongation or migration of fiber cells are represented by irregular or excessive suture branches. Also, the suture defects are believed to affect lens optical quality (48,49) and might lead to cataract development (33,50). The abnormal suture lines in the lenses of 1-month-old CRYAA N101D mice, compared with CRYAA WT mice, represented an early differentiation defect in fiber cells.…”

Section: Discussionmentioning

confidence: 99%

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

Gupta

Asomugha

Srivastava

2011

Journal of Biological Chemistry

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To elucidate the morphological and cellular changes due to introduction of a charge during development and the possible mechanism that underlies cataract development in humans as a consequence of an additional charge, we generated a transgenic mouse model mimicking deamidation of Asn at position 101. The mouse model expresses a human ␣A-crystallin gene in which Asn-101 was replaced with Asp, which is referred to as ␣AN101D-transgene and is considered to be "deamidated" in this study. Mice expressing ␣AN101D-transgene are referred to here CRYAA N101D mice. All of the lines showed the expression of ␣AN101D-transgene. Compared with the lenses of mice expressing wild-type (WT) ␣A-transgene (referred to as CRYAA WT mice), the lenses of CRYAA N101D mice showed (a) altered ␣A-crystallin membrane protein (aquaporin-0 (AQP0), a specific lens membrane protein) interaction, (b) extracellular spaces between outer cortical fiber cells, (c) attenuated denucleation during confocal microscopic examination, (d) disrupted normal fiber cell organization and structure during scanning electron microscopic examination, (e) distorted posterior suture lines by bright field microscopy, and (f) development of a mild anterior lens opacity in the superior cortical region during the optical coherence tomography scan analysis. Relative to lenses with WT ␣A-crystallin, the lenses containing the deamidated ␣A-crystallin also showed an aggregation of ␣A-crystallin and a higher level of water-insoluble proteins, suggesting that the morphological and cellular changes in these lenses are due to the N101D mutation. This study provides evidence for the first time that expression of deamidated ␣A-crystallin caused disruption of fiber cell structural integrity, protein aggregation, insolubilization, and mild cortical lens opacity.The ocular lens has a unique cellular architecture consisting of a single layer of cuboidal epithelial cells, which divide and differentiate at the equator into fiber cells (1). The fiber cells elongate, and they synthesize fiber cell-specific proteins, such as AQP0 (aquaporin-0)/MIP (main intrinsic protein), cytoskeletal proteins, and crystallins (1-4). As the new fiber cells are laid down at the lens equator, the older fiber cells are pushed toward the lens core and simultaneously lose their nuclei and organelles while exhibiting very little protein turnover. Among the three classes of the vertebrate lens crystallins (␣-, ␤-, and ␥-crystallins), ␣-crystallins are composed of two primary gene products, A and B, known as ␣A-and ␣B-crystallins, that show ϳ60% amino acid homology and constitute up to 50% of the total lens proteins. Both ␣A-and ␣B-crystallins belong to a family of small heat shock proteins with "chaperone" activity (5, 6). These crystallins are constitutively expressed in both lens epithelial and fiber cells (7) and undergo numerous age-related post-translational modifications (PTMs) 2 that lead to their unfolding, aggregation, and insolubilization. These PTMs eventually lead to accumulation of damaged crystal...

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Section: Discussionmentioning

confidence: 99%

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

Gupta

Asomugha

Srivastava

2011

Journal of Biological Chemistry

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“…These macrophages or neutrophils which also accompany inflammation could release superoxide, peroxide and hypochlorite into the vitreous. From the small vitreous space of the rat these damaging oxidative species could diffuse to the posterior of the lens where induced oxidative stress could lead to the transient cataracts observed in the RCS rat (Al-Ghoul, Novak and Kuzak, 1998). Since diabetes is known to damage both retina and lens, it is plausible that foreign proteins in the rat vitreous could originate from the lens or retina.…”

Section: In Vivo Dietary Supplementation During Longer-term Diabetes mentioning

confidence: 99%

Modelling Cortical Cataractogenesis 21: In Diabetic Rat Lenses Taurine Supplementation Partially Reduces Damage Resulting from Osmotic Compensation Leading to Osmolyte Loss and Antioxidant Depletion

Mitton

Linklater

Dzialoszynski

et al. 1999

Experimental Eye Research

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“…In this study an alteration in the posterior environment as a function of surgery (partial vitrectomy) resulted in subsequent ®ber formation with imprecise variations in posterior ®ber length and opposite end curvature, but without a concomitant effect on the same ®ber parameters anteriorly. In studies of Royal College of Surgeons Rats (RCS rats), an animal model for autosomal recessive retinitis pigmentosa (ARRP; Al-Ghoul, Novak and Al-Ghoul et al, 1999;Kuszak et al, 1999), retinal degeneration resulted in a speci®c failure to form normal posterior sutures while anterior suture formation occurred relatively normally. The factors that control or in¯u-ence the precise variation in ®ber length and opposite end curvature necessary to produce normal suture patterns throughout a lifetime of lens growth are unknown.…”

Section: Table IImentioning

confidence: 98%

The Relationship Between Rabbit Lens Optical Quality and Sutural Anatomy after Vitrectomy

Kuszak

Sivak

Herbert

et al. 2000

Experimental Eye Research

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The Structure Of Posterior Subcapsular Cataracts In The Royal College Of Surgeons (RCS) Rats

Cited by 32 publications

References 20 publications

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

Modelling Cortical Cataractogenesis 21: In Diabetic Rat Lenses Taurine Supplementation Partially Reduces Damage Resulting from Osmotic Compensation Leading to Osmolyte Loss and Antioxidant Depletion

The Relationship Between Rabbit Lens Optical Quality and Sutural Anatomy after Vitrectomy

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