“…Collagen type IV seems to have a special role in the stroma beyond its critical role as a major component of the epithelial basement membrane (EBM) and Descemet's membrane, along with its association with anchoring fibrils in the anterior stroma. Thus, in the normal unwounded cornea, collagen type IV is detected at high levels in the EBM 22 , 23 and Descemet's membrane, 24 , 25 ( Fig. 4 ) and at much lower levels associated with the anchoring fibrils.…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 89%
“…Note that the corneal endothelium and Descemet's membrane have not regenerated at this time point after injury. 25 ( G ) At 6 months after Descemetorhexis, the endothelium and Descemet's membrane have regenerated. 25 Collagen type IV ( green ) is present in the regenerated Descemet's membrane ( arrowhead ) and persists in the posterior stroma ( bracket ) after production by corneal fibroblasts.…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 99%
“… 25 ( G ) At 6 months after Descemetorhexis, the endothelium and Descemet's membrane have regenerated. 25 Collagen type IV ( green ) is present in the regenerated Descemet's membrane ( arrowhead ) and persists in the posterior stroma ( bracket ) after production by corneal fibroblasts. This area of the stroma is not yet repopulated with keratocytes (not shown).…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 99%
“…This area of the stroma is not yet repopulated with keratocytes (not shown). 25 e is epithelium in all panels. Blue is DAPI in all panels.…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 99%
“…( E ) Rabbit cornea at two weeks after 5 mm central 1 M sodium hydroxide exposure for 1 minute with severe fibrosis and CNV. ( F ) Rabbit cornea at 4 months after 8 mm Descemetorhexis removal of the central endothelium and Descemet's membrane with persistent stromal scarring fibrosis and CNV, but a decrease since the one-month time point (not shown but see Ref. 25 ).…”
Purpose
To highlight the cellular, matrix, and hydration changes associated with opacity that occurs in the corneal stroma after injury.
Methods
Review of the literature.
Results
The regulated transition of keratocytes to corneal fibroblasts and myofibroblasts, and of bone marrow-derived fibrocytes to myofibroblasts, is in large part modulated by transforming growth factor beta (TGFβ) entry into the stroma after injury to the epithelial basement membrane (EBM) and/or Descemet's membrane. The composition, stoichiometry, and organization of the stromal extracellular matrix components and water is altered by corneal fibroblast and myofibroblast production of large amounts of collagen type I and other extracellular matrix components—resulting in varying levels of stromal opacity, depending on the intensity of the healing response. Regeneration of EBM and/or Descemet's membrane, and stromal cell production of non-EBM collagen type IV, reestablishes control of TGFβ entry and activity, and triggers TGFβ-dependent myofibroblast apoptosis. Eventually, corneal fibroblasts also disappear, and repopulating keratocytes reorganize the disordered extracellular matrix to reestablish transparency.
Conclusions
Injuries to the cornea produce varying amounts of corneal opacity depending on the magnitude of cellular and molecular responses to injury. The EBM and Descemet's membrane are key regulators of stromal cellularity through their modulation of TGFβ. After injury to the cornea, depending on the severity of the insult, and possibly genetic factors, trace opacity to severe scarring fibrosis develops. Stromal cellularity, and the functions of different cell types, are the major determinants of the level of the stromal opacity.
“…Collagen type IV seems to have a special role in the stroma beyond its critical role as a major component of the epithelial basement membrane (EBM) and Descemet's membrane, along with its association with anchoring fibrils in the anterior stroma. Thus, in the normal unwounded cornea, collagen type IV is detected at high levels in the EBM 22 , 23 and Descemet's membrane, 24 , 25 ( Fig. 4 ) and at much lower levels associated with the anchoring fibrils.…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 89%
“…Note that the corneal endothelium and Descemet's membrane have not regenerated at this time point after injury. 25 ( G ) At 6 months after Descemetorhexis, the endothelium and Descemet's membrane have regenerated. 25 Collagen type IV ( green ) is present in the regenerated Descemet's membrane ( arrowhead ) and persists in the posterior stroma ( bracket ) after production by corneal fibroblasts.…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 99%
“… 25 ( G ) At 6 months after Descemetorhexis, the endothelium and Descemet's membrane have regenerated. 25 Collagen type IV ( green ) is present in the regenerated Descemet's membrane ( arrowhead ) and persists in the posterior stroma ( bracket ) after production by corneal fibroblasts. This area of the stroma is not yet repopulated with keratocytes (not shown).…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 99%
“…This area of the stroma is not yet repopulated with keratocytes (not shown). 25 e is epithelium in all panels. Blue is DAPI in all panels.…”
Section: Contributions Of Stromal Matrix Components To Transparencymentioning
confidence: 99%
“…( E ) Rabbit cornea at two weeks after 5 mm central 1 M sodium hydroxide exposure for 1 minute with severe fibrosis and CNV. ( F ) Rabbit cornea at 4 months after 8 mm Descemetorhexis removal of the central endothelium and Descemet's membrane with persistent stromal scarring fibrosis and CNV, but a decrease since the one-month time point (not shown but see Ref. 25 ).…”
Purpose
To highlight the cellular, matrix, and hydration changes associated with opacity that occurs in the corneal stroma after injury.
Methods
Review of the literature.
Results
The regulated transition of keratocytes to corneal fibroblasts and myofibroblasts, and of bone marrow-derived fibrocytes to myofibroblasts, is in large part modulated by transforming growth factor beta (TGFβ) entry into the stroma after injury to the epithelial basement membrane (EBM) and/or Descemet's membrane. The composition, stoichiometry, and organization of the stromal extracellular matrix components and water is altered by corneal fibroblast and myofibroblast production of large amounts of collagen type I and other extracellular matrix components—resulting in varying levels of stromal opacity, depending on the intensity of the healing response. Regeneration of EBM and/or Descemet's membrane, and stromal cell production of non-EBM collagen type IV, reestablishes control of TGFβ entry and activity, and triggers TGFβ-dependent myofibroblast apoptosis. Eventually, corneal fibroblasts also disappear, and repopulating keratocytes reorganize the disordered extracellular matrix to reestablish transparency.
Conclusions
Injuries to the cornea produce varying amounts of corneal opacity depending on the magnitude of cellular and molecular responses to injury. The EBM and Descemet's membrane are key regulators of stromal cellularity through their modulation of TGFβ. After injury to the cornea, depending on the severity of the insult, and possibly genetic factors, trace opacity to severe scarring fibrosis develops. Stromal cellularity, and the functions of different cell types, are the major determinants of the level of the stromal opacity.
Penetrating corneal wounds can cause severe vision impairment and require prompt intervention to restore globe integrity and minimize the risk of infection. Tissue adhesives have emerged as a promising alternative to suturing for mitigating postoperative complications. However, conventional water‐soluble adhesives suffer formidable challenges in sealing penetrating corneal wounds due to dilution or loss in a moist environment. Inspired by the robust adhesion of mussels in aquatic conditions, an injectable photocurable bioadhesive hydrogel (referred to as F20HD5) composed of polyether F127 diacrylate and dopamine‐modified hyaluronic acid methacrylate is developed for sutureless closure of corneal full‐thickness wounds. F20HD5 exhibits high transparency, wound‐sealing ability, proper viscosity, biodegradability, and excellent biocompatibility. It allows in situ cross‐linking via visible light, thereby providing sufficient mechanical strength and adhesiveness. In vivo, the adhesive hydrogel effectively closed penetrating linear corneal incisions and corneal injuries with minimal tissue loss in rabbits. During the 56‐day follow‐up, the hydrogel facilitates the repair of the injured corneas, resulting in more symmetrical curvatures and less scarring in distinction to the untreated control. Thus, bioinspired hydrogel holds promise as an effective adhesive for sealing full‐thickness corneal wounds.
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