Possible Mechanism of Exacerbating Cataract Formation in Cataractous Human Lens Capsules Induced by Systemic Hypertension or Glaucoma

Lee, Shui‐Mei; Lin, Shan‐Yang; Li, Mei-Jane; Liang, Run-Chu

doi:10.1159/000268001

Cited by 43 publications

(33 citation statements)

References 23 publications

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“…Only a few studies have provided evidence that the amyloid misfolding pathway may be physiologically relevant. For example, FTIR spectra of decapsulated cataract tissue exhibits an absorption at 1620 cm −1 , which is especially pronounced in cataract tissue taken from patients that suffer from glaucoma (77). This amide I frequency indicative of the extended vibrational coupling in amyloid β-sheets (Table 1) (49, 51).…”

Section: Discussionmentioning

confidence: 99%

Amyloid Fiber Formation in Human γD-Crystallin Induced by UV–B Photodamage

et al. 2013

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γD-crystallin is an abundant structural protein of the lens that is found in native and modified forms in cataractous aggregates. We establish that UV-B irradiation of γD-crystallin leads to structurally specific modifications and precipitation via two mechanisms: amorphous aggregates and amyloid fibers. UV-B radiation causes cleavage of the backbone, in large measure near the interdomain interface, where side chain oxidations are also concentrated. 2D IR spectroscopy and expressed protein ligation localize fiber formation exclusively to the C-terminal domain of γD-crystallin. The native β-sandwich domains are not retained upon precipitation by either mechanism. The similarity between the amyloid forming pathway when induced by either UV-B radiation or low pH suggests that it is the propensity for the C-terminal β-sandwich domain to form amyloid β-sheets that determines the misfolding pathway independent of the mechanism of denaturation.

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Section: Discussionmentioning

confidence: 99%

Amyloid Fiber Formation in Human γD-Crystallin Induced by UV–B Photodamage

et al. 2013

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“…To date, amyloid fibers have not been observed in protein aggregates taken from cataractous lenses, despite the apparent high propensity for crystallins to form amyloid fibers in vitro . However, in a few cases where the infrared spectra of such aggregates have been measured, low‐frequency absorption near 1620 cm −1 , which is characteristic of extended amyloid β‐sheets, have been reported . The fact that such spectral features are observed for aggregates that form sheets instead of fibers indicates that amyloid‐like aggregation may occur even where fibers are not observed.…”

Section: Discussionmentioning

confidence: 99%

“…1,7,[11][12][13][14][15][16]20,25,73 However, in a few cases where the infrared spectra of such aggregates have been measured, lowfrequency absorption near 1620 cm 21 , which is characteristic of extended amyloid b-sheets, have been reported. 74 The fact that such spectral features are observed for aggregates that form sheets instead of fibers indicates that amyloid-like aggregation may occur even where fibers are not observed. In fact, amyloid-like infrared spectra of g-crystallins, without the presence of fiber morphology in TEM images, has been observed in vitro.…”

Section: Discussionmentioning

confidence: 99%

An alternative structural isoform in amyloid‐like aggregates formed from thermally denatured human γD‐crystallin

2014

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The eye lens protein cD-crystallin contributes to cataract formation in the lens. In vitro experiments show that cD-crystallin has a high propensity to form amyloid fibers when denatured, and that denaturation by acid or UV-B photodamage results in its C-terminal domain forming the b-sheet core of amyloid fibers. Here, we show that thermal denaturation results in sheet-like aggregates that contain cross-linked oligomers of the protein, according to transmission electron microscopy and SDS-PAGE. We use two-dimensional infrared spectroscopy to show that these aggregates have an amyloid-like secondary structure with extended b-sheets, and use isotope dilution experiments to show that each protein contributes approximately one b-strand to each b-sheet in the aggregates. Using segmental 13 C labeling, we show that the organization of the protein's two domains in thermally induced aggregates results in a previously unobserved structure in which both the N-terminal and C-terminal domains contribute to b-sheets. We propose a model for the structural organization of the aggregates and attribute the recruitment of the N-terminal domain into the fiber structure to intermolecular cross linking.

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“…Elevated IOP is the most crucial risk factor for glaucoma, and a sufficiently high IOP level can cause ocular tissue damage [7,8]. The study has reported that systemic hypertension or glaucoma might change the protein secondary structures of the immature cataractous lens capsule and alter ionic transport through the deformed lens capsule [9]. Therefore, protein expression alterations in various intraocular tissues, including the cornea, conjunctiva, uvea (composed of the iris, ciliary body, and choroid), retina, and sclera, during ischemia–reperfusion (IR) injury, may play a crucial role in clinical ophthalmology.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Various Rat Ocular Tissues after Ischemia–Reperfusion Injury and Possible Relevance to Acute Glaucoma

Chen

Chou

Chang

et al. 2017

IJMS

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Glaucoma is a group of eye diseases that can cause vision loss and optical nerve damage. To investigate the protein expression alterations in various intraocular tissues (i.e., the cornea, conjunctiva, uvea, retina, and sclera) during ischemia–reperfusion (IR) injury, this study performed a proteomic analysis to qualitatively investigate such alterations resulting from acute glaucoma. The IR injury model combined with the proteomic analysis approach of two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to monitor the protein expression alterations in two groups of specimens (an IR injury group and a control group). The analysis results revealed 221 unique differentially expressed proteins of a total of 1481 proteins in the cornea between the two groups. In addition, 97 of 1206 conjunctival proteins, 90 of 1354 uveal proteins, 61 of 1180 scleral proteins, and 37 of 1204 retinal proteins were differentially expressed. These findings imply that different ocular tissues have different tolerances against IR injury. To sum up, this study utilized the acute glaucoma model combined with 2D-DIGE and MALDI-TOF MS to investigate the IR injury affected protein expression on various ocular tissues, and based on the ratio of protein expression alterations, the alterations in the ocular tissues were in the following order: the cornea, conjunctiva, uvea, sclera, and retina.

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Possible Mechanism of Exacerbating Cataract Formation in Cataractous Human Lens Capsules Induced by Systemic Hypertension or Glaucoma

Cited by 43 publications

References 23 publications

Amyloid Fiber Formation in Human γD-Crystallin Induced by UV–B Photodamage

Amyloid Fiber Formation in Human γD-Crystallin Induced by UV–B Photodamage

An alternative structural isoform in amyloid‐like aggregates formed from thermally denatured human γD‐crystallin

Proteomic Analysis of Various Rat Ocular Tissues after Ischemia–Reperfusion Injury and Possible Relevance to Acute Glaucoma

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