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Review
. 2023 Jun 15;12(2):48.
doi: 10.3390/biotech12020048.

Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art

Affiliations
Review

Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art

Matteo Posarelli et al. BioTech (Basel). .

Abstract

The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.

Keywords: amniotic membrane; autologous serum tear; dry-eye disease; limbal stem cells; neurotrophic keratopathy; ocular-surface disease; tissue regeneration.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Dry-eye keratopathy in a patient with Sjögren’s syndrome; (b) advanced pterygium encroaching on the visual axis; (c) neurotrophic corneal ulcer associated with diffuse corneal fluorescein staining; and (d) full corneal conjunctivalization in limbal stem-cell deficiency six months after a chemical injury.
Figure 2
Figure 2
(A) Corneal perforation in an advanced neurotrophic ulcer; (B) corneal debulking during the early phases of surgical management: penetrating keratoplasty + open sky cataract extraction + amniotic membrane transplant (Omnigen®); (C) dry amniotic membrane (Omnigen®) apposition on the completed penetrating keratoplasty; and (D) amniotic membrane sutured on the ocular surface as a graft using a 10/0 absorbable (Vicryl) continuous suture.
Figure 3
Figure 3
Limbal stem cell deficiency (LSCD) is associated with corneal epithelial abnormalities (A), corneal conjunctivalization and neovascularization (B), corneal scarring, and chronic inflammation.
Figure 4
Figure 4
The Boston keratoprosthesis (KPro) Type 1 in a patient with bilateral total limbal stem-cell deficiency (LSCD).
Figure 5
Figure 5
Anterior segment OCT (AS-OCT) showing an abnormal corneal morphology in Fuchs endothelial dystrophy. The corneal stroma is edematous with a central corneal thickness of 638 microns and posterior stromal ripples.
Figure 6
Figure 6
(A) Slit lamp photo showing active ocular mucous membrane pemphigoid: ocular inflammation, shortening of the fornix, and symblepharon; and (B) advanced ocular mucous membrane pemphigoid with severe ocular-surface neovascularization, corneal ulcer, and trichiasis.

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