Keratoconus Experimentally Produced in the Rat by Vitamin a Deficiency

Mutch, J. R.; Richards, Marion B.

doi:10.1136/bjo.23.6.381

Cited by 11 publications

(7 citation statements)

References 1 publication

(1 reference statement)

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“…Adult vitamin A deficiency has been implicated in abnormal corneal structure and function, and has been suggested to contribute to the onset and progression of corneal diseases such as xerophthalmia (McLaren and Frigg, 2001) and keratoconus (Mutch and Richards, 1939). However, a requirement for the endogenous vitamin A metabolite RA in corneal maintenance has not previously been reported.…”

mentioning

confidence: 99%

Endogenous retinoic acid signaling is required for maintenance and regeneration of cornea

Kumar

Dollé

Ghyselinck

et al. 2017

Experimental Eye Research

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Retinoic acid (RA) is a biologically active metabolite of vitamin A (retinol) that serves as an important signaling molecule in orchestrating diverse developmental processes including multiple roles during ocular development. Loss-of-function studies using gene knockouts of RA-synthesizing enzymes encoded by Aldh1a1, Aldh1a2, and Aldh1a3 (also known as Raldh1, Raldh2, and Raldh3) have provided valuable insight into how RA controls eye morphogenesis including corneal development, however it is unclear whether endogenous RA is required for maintenance and regeneration of adult cornea. Here, we investigated the role of Aldh1a genes in the adult cornea using a novel conditional Aldh1a1,2,3-flox/flox;Rosa26-CreERT2 loss-of-function mouse model to determine the biological function of RA. Our findings indicate that loss of RA synthesis results in corneal thinning characterized by reduced thickness of the stromal layer, impaired corneal epithelial cell proliferation, and increased apoptosis. Corneal thinning in Aldh1a-deficient mice was significantly rescued by RA administration, indicating an important role of endogenous RA signaling in adult corneal homeostasis and regeneration. Thus, Aldh1a1,2,3-flox/flox;Rosa26-CreERT2 mice provide a useful model for investigating the mechanistic role of RA signaling in adult corneal maintenance and could provide new insights into therapeutic approaches for controlling corneal repair to prevent vision loss.

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mentioning

confidence: 99%

Endogenous retinoic acid signaling is required for maintenance and regeneration of cornea

Kumar

Dollé

Ghyselinck

et al. 2017

Experimental Eye Research

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“…Furthermore, there are no genetic or spontaneous models. Multiple experiments report inducing some degree of KC in rats using a variety of treatments, including UVR, SAL003, and vitamin A deficiency [40][41][42].…”

Section: Rat Modelsmentioning

confidence: 99%

“…A study by Mutch et al from 1939 asserted that KC could be induced through vitamin A deficiency in the corneas of rats [42]. Earlier studies identified keratoconus as an unintended result during experiments using vitamin-A-deficient rats [88].…”

Section: Treatment-induced Rat Modelsmentioning

confidence: 99%

“…Earlier studies identified keratoconus as an unintended result during experiments using vitamin-A-deficient rats [88]. To directly assess keratoconus in vitamin-A-deficient rats, 30 rats were subjected to a vitamin-A-free diet [42]. Some rats suffered from several ocular afflictions, including xerophthalmia, perforation, and keratoconus, which varied in severity [42].…”

Section: Treatment-induced Rat Modelsmentioning

confidence: 99%

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Animal Models for the Study of Keratoconus

Hadvina,

Estes,

Liu

2023

Cells

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Keratoconus (KC) is characterized by localized, central thinning and cone-like protrusion of the cornea. Its precise etiology remains undetermined, although both genetic and environmental factors are known to contribute to disease susceptibility. Due to KC’s complex nature, there is currently no ideal animal model to represent both the corneal phenotype and underlying pathophysiology. Attempts to establish a KC model have involved mice, rats, and rabbits, with some additional novel animals suggested. Genetic animal models have only been attempted in mice. Similarly, spontaneously occurring animal models for KC have only been discovered in mice. Models generated using chemical or environmental treatments have been attempted in mice, rats, and rabbits. Among several methods used to induce KC in animals, ultraviolet radiation exposure and treatment with collagenase are some of the most prevalent. There is a clear need for an experimental model animal to elucidate the underlying mechanisms behind the development and progression of keratoconus. An appropriate animal model could also aid in the development of treatments to slow or arrest the disorder.

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“…Vitamin A (Vit A) deficiency was also suspected to contribute to KC development [55]. Recently, it has been shown that retinoic acid supplementation, an active metabolite from Vit A, promotes corneal crosslinking by upregulating transglutaminase-2 (TG2) expression in corneal epithelium and keratocyte [56].…”

Section: Vitaminsmentioning

confidence: 99%

Nutritional and Metabolic Imbalance in Keratoconus

et al. 2022

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Keratoconus (KC) is a progressive corneal degeneration characterized by structural changes consisting of progressive thinning and steepening of the cornea. These alterations result in biomechanical weakening and, clinically, in vision loss. While the etiology of KC has been the object of study for over a century, no single agent has been found. Recent reviews suggest that KC is a multifactorial disease that is associated with a wide variety of genetic and environmental factors. While KC is typically considered a disease of the cornea, associations with systemic conditions have been well described over the years. In particular, nutritional and metabolic imbalance, such as the redox status, hormones, metabolites, and micronutrients (vitamins and metal ions), can deeply influence KC initiation and progression. In this paper, we comprehensively review the different nutritional (vitamins and minerals) and metabolic (hormones and metabolites) factors that are altered in KC, discussing their possible implication in the pathophysiology of the disease.

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Keratoconus Experimentally Produced in the Rat by Vitamin a Deficiency

Cited by 11 publications

References 1 publication

Endogenous retinoic acid signaling is required for maintenance and regeneration of cornea

Endogenous retinoic acid signaling is required for maintenance and regeneration of cornea

Animal Models for the Study of Keratoconus

Nutritional and Metabolic Imbalance in Keratoconus

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