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Mechanism of Cell Signaling during Eye Development and Diseases

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 7579

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Special Issue Editors

Dr. Mehrnoosh Saghizadeh Ghiam

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Guest Editor

Board of Governors Regenerative Medicine Institute, Eye Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Interests: diabetic cornea; limbal stem cells; microRNA; extracellular vesicles/exosomes; wound healing; gene therapy; stem cell therapy; corneal epithelial regeneration; intercellular communication
Special Issues, Collections and Topics in MDPI journals

Dr. Vivien Coulson-Thomas

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Guest Editor

The Ocular Surface Institute (TOSI) Health and Biomedical Sciences Building, College of Optometry, University of Houston, Houston, TX, USA
Interests: extracellular matrix; corneal development and wound healing; limbal stem cells; stem cell therapy; corneal regeneration; dry eye disease; meibomian gland dysfunction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cell signaling pathways are important in mediating essential processes in embryonic eye development and adult tissues. Their coordination and integration are critical for mediating processes ranging from cell proliferation and differentiation to cell fate determination and polarity. Cellular communication is compelled by these pathways and is driven by hormones, transcription factors, or other signaling molecules.

Several major signaling pathways in eye development such as Hedgehog, Wnt, retinoic acid, FGF, TGF-β, and Notch operate during development, in a precise temporal and spatial patterning in the embryo and in adult tissues, generating diverse cellular responses in a cell-type-specific manner. Altered expressions of these pathways can lead to a large number of eye diseases, such as photoreceptor degeneration as a result of dysregulated Wnt signaling pathway, Glaucoma as a result of altered TGF-β signaling, and pathological angiogenesis-related eye disorders due to defects in Notch signaling.

Therefore, delineating the mechanisms of cell signaling during eye development and disease can unveil their potential as targets for novel therapeutic strategies for the treatment of ocular diseases.

Dr. Mehrnoosh Saghizadeh Ghiam
Dr. Vivien Coulson-Thomas
Guest Editors

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Keywords

cell signaling
ocular
eye disorders
Wnt signaling
TGF-β

Published Papers (5 papers)

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Research

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15 pages, 12230 KiB

Open AccessArticle

Chemical (Alkali) Burn-Induced Neurotrophic Keratitis Model in New Zealand Rabbit Investigated Using Medical Clinical Readouts and In Vivo Confocal Microscopy (IVCM)

by Mehak Vohra, Abha Gour, Jyoti Rajput, Bharti Sangwan, Monika Chauhan, Kartik Goel, Ajith Kamath, Umang Mathur, Arun Chandru, Virender Singh Sangwan, Tuhin Bhowmick and Anil Tiwari

Cells 2024, 13(5), 379; https://doi.org/10.3390/cells13050379 - 22 Feb 2024

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Abstract

Purpose: Chemical eye injury is an acute emergency that can result in vision loss. Neurotrophic keratitis (NK) is the most common long-term manifestation of chemical injury. NK due to alkali burn affects ocular surface health and is one of its most common causes. Here, we established a rabbit model of corneal alkali burns to evaluate the severity of NK-associated changes. Material methods: Alkali burns were induced in NZ rabbits by treating the cornea with (i) a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (Mild NK) and (ii) trephination using a guarded trephine (5 mm diameter and 150-micron depth), followed by alkali burn, with a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (a severe form of NK). Immediately after, the cornea was rinsed with 10 mL of normal saline to remove traces of NaOH. Clinical features were evaluated on Day 0, Day 1, Day 7, Day 15, and Day 21 post-alkali burn using a slit lamp, Pentacam, and anterior segment optical coherence tomography (AS-OCT). NK-like changes in epithelium, sub-basal nerve plexus, and stroma were observed using in vivo confocal microscopy (IVCM), and corneal sensation were measured using an aesthesiometer post alkali injury. After 21 days, pro-inflammatory cytokines were evaluated for inflammation through ELISA. Results: Trephination followed by alkali burn resulted in the loss of epithelial layers (manifested using fluorescein stain), extensive edema, and increased corneal thickness (550 µm compared to 380 µm thickness of control) evaluated through AS-OCT and increased opacity score in alkali-treated rabbit (80 compared to 16 controls). IVCM images showed complete loss of nerve fibers, which failed to regenerate over 30 days, and loss of corneal sensation—conditions associated with NK. Cytokines evaluation of IL6, VEGF, and MMP9 indicated an increased angiogenic and pro-inflammatory milieu compared to the milder form of NK and the control. Discussion: Using clinical parameters, we demonstrated that the alkali-treated rabbit model depicts features of NK. Using IVCM in the NaOH burn animal model, we demonstrated a complete loss of nerve fibers with poor self-healing capability associated with sub-basal nerve degeneration and compromised corneal sensation. This pre-clinical rabbit model has implications for future pre-clinical research in neurotrophic keratitis. Full article

(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)

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23 pages, 14033 KiB

Open AccessArticle

Conditional Ablation of Spred1 and Spred2 in the Eye Lens Negatively Impacts Its Development and Growth

by Fatima Wazin and Frank J. Lovicu

Cells 2024, 13(4), 290; https://doi.org/10.3390/cells13040290 - 6 Feb 2024

Viewed by 682

Abstract

The development and growth of the eye depends on normal lens morphogenesis and its growth. This growth, in turn, is dependent on coordinated proliferation of the lens epithelial cells and their subsequent differentiation into fiber cells. These cellular processes are tightly regulated to maintain the precise cellular structure and size of the lens, critical for its transparency and refractive properties. Growth factor-mediated MAPK signaling driven by ERK1/2 has been reported as essential for regulating cellular processes of the lens, with ERK1/2 signaling tightly regulated by endogenous antagonists, including members of the Sprouty and related Spred families. Our previous studies have demonstrated the importance of both these inhibitory molecules in lens and eye development. In this study, we build on these findings to highlight the importance of Spreds in regulating early lens morphogenesis by modulating ERK1/2-mediated lens epithelial cell proliferation and fiber differentiation. Conditional loss of both Spred1 and Spred2 in early lens morphogenesis results in elevated ERK1/2 phosphorylation, hyperproliferation of lens epithelia, and an associated increase in the rate of fiber differentiation. This results in transient microphakia and microphthalmia, which disappears, owing potentially to compensatory Sprouty expression. Our data support an important temporal role for Spreds in the early stages of lens morphogenesis and highlight how negative regulation of ERK1/2 signaling is critical for maintaining lens proliferation and fiber differentiation in situ throughout life. Full article

(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)

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13 pages, 3144 KiB

Open AccessArticle

Altered Visual Function in Short-Wave-Sensitive 1 (sws1) Gene Knockout Japanese Medaka (Oryzias latipes) Larvae

by Ke Lu, Jiaqi Wu, Shulin Tang, Yuye Wang, Lixin Zhang, Farui Chai and Xu-Fang Liang

Cells 2023, 12(17), 2157; https://doi.org/10.3390/cells12172157 - 28 Aug 2023

Viewed by 1071

Abstract

Visual perception plays a crucial role in foraging, avoiding predators, mate selection, and communication. The regulation of color vision is largely dependent on opsin, which is the first step in the formation of the visual transduction cascade in photoreceptor cells. Short-wave-sensitive 1 (sws1) is a visual pigment that mediates short-wavelength light transduction in vertebrates. The depletion of sws1 resulted in increased M-opsin in mice. However, there is still no report on the visual function of sws1 in teleost fish. Here, we constructed the sws1 knockout medaka using CRISPR/Cas9 technology. The 6 dph (days post-hatching) medaka sws1^−/− larvae exhibited significantly decreased food intake and total length at the first feeding stage, and the mRNA levels of orexigenic genes (npy and agrp) were significantly upregulated after feeding. The swimming speed was significantly reduced during the period of dark-light transition stimulation in the sws1-mutant larvae. Histological analysis showed that the thickness of the lens was reduced, whereas the thickness of the ganglion cell layer (GCL) was significantly increased in sws1^−/− medaka larvae. Additionally, the deletion of sws1 decreased the mRNA levels of genes involved in phototransduction (gnb3b, grk7a, grk7b, and pde6c). We also observed increased retinal cell apoptosis and oxidative stress in sws1 knockout medaka larvae. Collectively, these results suggest that sws1 deficiency in medaka larvae may impair visual function and cause retinal cell apoptosis, which is associated with the downregulation of photoconduction expression and oxidative stress. Full article

(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)

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Review

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16 pages, 1504 KiB

Open AccessReview

The Molecular Mechanisms Responsible for Tear Hyperosmolarity-Induced Pathological Changes in the Eyes of Dry Eye Disease Patients

by Carl Randall Harrell, Lisa Feulner, Valentin Djonov, Dragica Pavlovic and Vladislav Volarevic

Cells 2023, 12(23), 2755; https://doi.org/10.3390/cells12232755 - 1 Dec 2023

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Abstract

Dry eye disease (DED) is a multifactorial disorder of the lacrimal system and ocular surface, characterized by a deficiency in the quality and/or quantity of the tear fluid. The multifactorial nature of DED encompasses a number of interconnected underlying pathologies, including loss of homeostasis, instability and hyperosmolarity of the tears, and the induction and propagation of detrimental inflammatory responses in the eyes, which finally results in the development of neurosensory dysfunction and visual disruption. Dryness, grittiness, scratchiness, discomfort, inflammation, burning, watering, ocular fatigue, pain, and decreased functional visual acuity are common symptoms of DED. Eye dysfunction drastically attenuates patients’ quality of life. Accordingly, a better understanding of the pathogenic processes that regulate the development and progression of DED is crucially important for the establishment of new and more effective DED-related treatment approaches, which would significantly improve the quality of life of DED patients. Since the process of osmoregulation, which guards the ocular surface epithelia and maintains normal vision, is affected when the osmolarity of the tears is greater than that of the epithelial cells, tear hyperosmolarity (THO) is considered an initial, important step in the development, progression, and aggravation of DED. In order to delineate the role of THO in the pathogenesis of DED, in this review article, we summarize current knowledge related to the molecular mechanisms responsible for the development of THO-induced pathological changes in the eyes of DED patients, and we briefly discuss the therapeutic potential of hypo-osmotic eye drops in DED treatment. Full article

(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)

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20 pages, 2385 KiB

Open AccessReview

Limbal Epithelial Stem Cells in the Diabetic Cornea

by Lamia Nureen and Nick Di Girolamo

Cells 2023, 12(20), 2458; https://doi.org/10.3390/cells12202458 - 16 Oct 2023

Cited by 1 | Viewed by 1506

Abstract

Continuous replenishment of the corneal epithelium is pivotal for maintaining optical transparency and achieving optimal visual perception. This dynamic process is driven by limbal epithelial stem cells (LESCs) located at the junction between the cornea and conjunctiva, which is otherwise known as the limbus. In patients afflicted with diabetes, hyperglycemia-induced impairments in corneal epithelial regeneration results in persistent epithelial and other defects on the ocular surface, termed diabetic keratopathy (DK), which progressively diminish vision and quality of life. Reports of delayed corneal wound healing and the reduced expression of putative stem cell markers in diabetic relative to healthy eyes suggest that the pathogenesis of DK may be associated with the abnormal activity of LESCs. However, the precise role of these cells in diabetic corneal disease is poorly understood and yet to be comprehensively explored. Herein, we review existing literature highlighting aberrant LESC activity in diabetes, focusing on factors that influence their form and function, and emerging therapies to correct these defects. The consequences of malfunctioning or depleted LESC stocks in DK and limbal stem cell deficiency (LSCD) are also discussed. These insights could be exploited to identify novel targets for improving the management of ocular surface complications that manifest in patients with diabetes. Full article

(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)

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