Epithelial Cell, Keratocyte, and Endothelial Cell Apoptosis in Fuchs' Dystrophy and in Pseudophakic Bullous Keratopathy

Szentmáry, Nóra; Szende, B.; Süveges, Ildikó

doi:10.1177/112067210501500103

Cited by 37 publications

(22 citation statements)

References 17 publications

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“…48 Subsequent studies with TUNEL assay of entire corneas revealed significantly higher apoptotic cell numbers not only in the corneal endothelium but also in the stroma and epithelium in patients with FCD compared to controls. 49 Serial analysis of gene expression reveals decreased transcription levels of antioxidant molecules in FCD-affected corneal endothelium, including glutathione S-transferase-pi. 27 A number of apoptosis-related factors are found more frequently in FECD-affected corneas.…”

Section: Oxidative Damage and Apoptosismentioning

confidence: 99%

Fuchs Corneal Dystrophy

Eghrari

Riazuddin

Gottsch

2015

Progress in Molecular Biology and Translational Science

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Section: Oxidative Damage and Apoptosismentioning

confidence: 99%

Fuchs Corneal Dystrophy

Eghrari

Riazuddin

Gottsch

2015

Progress in Molecular Biology and Translational Science

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“…25 Various causative factors such as excessive phacoemulsification energy 26 and mechanical trauma 27 to the corneal endothelium during cataract extraction surgery have been implicated in causing stress-induced apoptosis of CECs. 28 Although PBK is characterized by diffuse damage to the corneal endothelial layer, 29 a peripheral rim of healthy CECs and DM is usually retained in corneas affected by FED. 22 As such, it has been postulated that this reservoir of healthy CECs in FED corneas can potentially be exploited to repopulate the centrally diseased corneal endothelium either by migration or proliferation, on exposure to externally applied stimulants.…”

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confidence: 99%

Predicative Factors for Corneal Endothelial Cell Migration

Soh

Peh

George

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To characterize the effects of Descemet's stripping, Rho-associated protein kinase inhibitor Y-27632, and donor age on endothelial migration in human corneas maintained in ex vivo culture.METHODS. Twenty-eight cadaveric human corneas underwent ex vivo culture in either standard or Y-27632-supplemented culture medium for 14 days. The posterior surface of each cornea was manipulated to create two types of wounds: scratched wound-corneal endothelial cells (CECs) were denuded from the Descemet's membrane (DM) to leave behind a bare but intact DM; and peeled wound-both the DM and overlying CECs were stripped to leave behind bare corneal stroma. Endothelial migration was assessed via Trypan blue staining. Morphologic traits of CECs were assessed via Alizarin red microscopy and scanning electron microscopy.RESULTS. The CECs migrated preferentially over scratched wounds compared with peeled wounds. Y-27632 supplementation accelerated endothelial migration over scratched wounds. Endothelial migration decreased with advanced donor age for both wound types, regardless of exposure to Y-27632. Y-27632 supplementation resulted in a less rapid decline in endothelial migration for donors older than 50 years of age for scratched surfaces. Greater cell density and hexagonality was observed over scratched wounds compared with peeled wounds, regardless of Y-27632 supplementation.CONCLUSIONS. The presence of an intact DM, Y-27632 supplementation, and young donor age are factors that promote endothelial migration in an ex vivo human cornea culture model. The negative effect of age on endothelial migration can be mitigated by the presence of an intact DM and Y-27632 supplementation.

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“…Recent data show that 15,707 (21.7%) of the 72,465 corneas provided by eye banks in the United States were used to treat FECD. 2 Histological analysis has suggested that the corneal endothelial cell (CEC) loss occurring in FECD is due to apoptosis, [3][4][5] but the pathophysiologic cause of this apoptosis has not been identified. In 2010, Engler and colleagues 6 showed morphological alterations of the endoplasmic reticulum (ER), and upregulation of markers of the unfolded protein response (UPR), such as glucose-regulated protein (GRP78), a subunit of eukaryotic initiation factor 2 (eIF2a), and CCAAT-enhancerbinding protein homologous protein (CHOP) in the corneal endothelium of FECD patients.…”

mentioning

confidence: 99%

Sustained Activation of the Unfolded Protein Response Induces Cell Death in Fuchs' Endothelial Corneal Dystrophy

Okumura

Kitahara

Okuda

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Okumura N, Kitahara M, Okuda H, et al. Sustained activation of the unfolded protein response induces cell death in Fuchs' endothelial corneal dystrophy. Invest Ophthalmol Vis Sci. 2017;58:3697-3707. DOI: 10.1167/iovs.16-21023 PURPOSE. The unfolded protein response (UPR) is believed to play a role in the pathogenesis of Fuchs' endothelial corneal dystrophy (FECD). The purpose of this study was to investigate whether unfolded proteins accumulate in the corneal endothelium in FECD and if they are involved in triggering cell death. METHODS.Descemet's membranes with corneal endothelial cells (CECs) were obtained during keratoplasty, and expression of aggresomes, type 1 collagen, fibronectin, and agrin was evaluated. Endoplasmic reticulum (ER) stress of immortalized human CECs from non-FECD subjects and from FECD patients (iHCEC and iFECD, respectively) were evaluated. The effect of MG132-mediated aggresome formation on the UPR and intrinsic pathway and the effect of mitochondrial damage on UPR were also examined. The effect of CHOP knockdown on the ER stress-mediated intrinsic pathway was also evaluated.RESULTS. Aggresome formation was higher in iFECD than in iHCEC and was colocalized with type 1 collagen, fibronectin, and agrin. GRP78, phosphorylated IRE1, PERK, and CHOP showed higher activation in iFECD than in iHCEC. MG132-mediated aggresome formation upregulated ER stress sensors, the mitochondrial membrane potential drop, cytochrome c release to the cytoplasm, and activation of caspase-9 and -3. By contrast, staurosporinemediated mitochondrial damage did not induce ER stress. Knockdown of CHOP attenuated the ER stress-induced cleavage of caspase-9, which is caused by intrinsic pathway activation.CONCLUSIONS. Excessive synthesis of extracellular matrix proteins induced unfolded protein accumulation in FECD. Prolonged ER stress-mediated cell death, occurring via the intrinsic apoptotic signaling pathway, therefore might be associated with the pathogenesis of FECD.

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Epithelial Cell, Keratocyte, and Endothelial Cell Apoptosis in Fuchs' Dystrophy and in Pseudophakic Bullous Keratopathy

Abstract: Apoptosis may play a role in the pathomechanism of Fuchs' dystrophy and in keratocyte death in corneas with PBK.

Cited by 37 publications

References 17 publications

Fuchs Corneal Dystrophy

Fuchs Corneal Dystrophy

Predicative Factors for Corneal Endothelial Cell Migration

Sustained Activation of the Unfolded Protein Response Induces Cell Death in Fuchs' Endothelial Corneal Dystrophy

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