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1.
Cells ; 12(9)2023 05 01.
Article in English | MEDLINE | ID: mdl-37174694

ABSTRACT

Limbal stem cell deficiency (LSCD) is a debilitating ocular surface disease that eventuates from a depleted or dysfunctional limbal epithelial stem cell (LESC) pool, resulting in corneal epithelial failure and blindness. The leading cause of LSCD is a chemical burn, with alkali substances being the most common inciting agents. Characteristic features of alkali-induced LSCD include corneal conjunctivalization, inflammation, neovascularization and fibrosis. Over the past decades, animal models of corneal alkali burn and alkali-induced LSCD have been instrumental in improving our understanding of the pathophysiological mechanisms responsible for disease development. Through these paradigms, important insights have been gained with regards to signaling pathways that drive inflammation, neovascularization and fibrosis, including NF-κB, ERK, p38 MAPK, JNK, STAT3, PI3K/AKT, mTOR and WNT/ß-catenin cascades. Nonetheless, the molecular and cellular events that underpin re-epithelialization and those that govern long-term epithelial behavior are poorly understood. This review provides an overview of the current mechanistic insights into the pathophysiology of alkali-induced LSCD. Moreover, we highlight limitations regarding existing animal models and knowledge gaps which, if addressed, would facilitate development of more efficacious therapeutic strategies for patients with alkali-induced LSCD.


Subject(s)
Limbal Stem Cell Deficiency , Limbus Corneae , Animals , Limbal Stem Cells , Phosphatidylinositol 3-Kinases/metabolism , Stem Cells/metabolism , Inflammation/pathology , Models, Animal
2.
Ophthalmic Surg Lasers Imaging Retina ; 48(9): 711-716, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28902331

ABSTRACT

BACKGROUND AND OBJECTIVE: To identify qualitative and quantitative features of spectral-domain optical coherence tomography (SD-OCT) as prognostic indicators of visual acuity (VA) loss in patients with choroideremia (CHM). PATIENTS AND METHODS: Retrospective study of 57 male patients with CHM. Central foveal thickness (CFT), subfoveal choroidal thickness (SCT), fundus autofluorescence area, and evidence of outer retinal and choroidal degeneration were analyzed by SD-OCT. RESULTS: Best-corrected VA logMAR at baseline was associated with CFT at baseline (r = -0.47; P < .01), CFT at most recent follow-up (r = -0.27; P < .01), and SCT at baseline (r = -0.31; P < .01). Ellipsoid zone (EZ) rupture was associated with a higher CFT loss (r = 0.33; P < .01) and macular cystic spaces (MCS) with a reduction in VA over time (hazard risk = 0.48; P = .05). CONCLUSION: Reduced CFT at baseline, EZ rupture, and MCS are poor prognostic indicators for VA outcome. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:711-716.].


Subject(s)
Choroideremia/pathology , Adolescent , Adult , Aged , Child , Choroid/pathology , Choroideremia/diagnostic imaging , Choroideremia/physiopathology , Female , Fovea Centralis/pathology , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retina/pathology , Retrospective Studies , Tomography, Optical Coherence/methods , Visual Acuity/physiology , Young Adult
3.
Zebrafish ; 14(2): 118-125, 2017 04.
Article in English | MEDLINE | ID: mdl-28051361

ABSTRACT

The present study outlines a protocol for examining retinal structure in zebrafish, a popular model organism for ocular studies, using spectral domain optical coherence tomography (SD-OCT). We demonstrate how this live imaging modality can be used to obtain high quality images of several retinal features, including the optic nerve, retinal vasculature, and the cone photoreceptor mosaic. Retinal histology sections were obtained from imaged fish for comparison with SD-OCT cross-sectional B-scans. Voronoi domain analysis was used to assess cone photoreceptor packing regularity at 3, 6, and 12 months. SD-OCT is an effective in vivo technique for studying the adult zebrafish retina and can be applied to disease models for longitudinal serial monitoring.


Subject(s)
Photoreceptor Cells/cytology , Tomography, Optical Coherence/methods , Zebrafish , Animals
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