transforming-growth-factor-beta and Corneal-Ulcer

Healing of ocular surface wounds is a complex process involving migration, mitosis, and differentiation of epithelial and stromal cells. Endogenously produced peptide growth factors such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), or transforming growth factor beta (TGF-beta) may play key roles in the natural wound healing process. Lacrimal gland cells were reported to synthesize and secrete EGF into tear fluid where it may enhance healing of corneal epithelial and stromal injuries by an exocrine pathway. EGF stimulated DNA synthesis of epithelial cells and stromal fibroblasts in culture, stimulated synthesis of fibronectin by epithelial cells and was chemotactic for human epithelial and stromal cells. Human corneal epithelial cells also synthesized TGF-alpha which may influence epithelial cells by an autocrine pathway. TGF-beta, which is a potent inducer of lysyl oxidase mRNA levels in cultures of human scleral fibroblasts, may be the factor most responsible for inducing synthesis of corneal extracellular matrix components after an injury. Treatment of epithelial injuries ocular surface wounds with exogenous peptide growth factors also accelerated healing in rabbits and primates. Treatment of severe ocular surface injuries caused by alkali with a combination of EGF, fibronectin, a synthetic collagenase inhibitor, and Aprotinin significantly blocked ulceration and enhanced epithelial regeneration. Clinical trials of topical treatment of EGF for ocular surface wounds suggest that peptide growth factors may be a valuable adjuvant for treatment of ocular surface wounds.

Topics: Animals; Cell Differentiation; Cell Movement; Cornea; Corneal Stroma; Corneal Ulcer; Epidermal Growth Factor; Epithelium; Humans; Mitosis; Transforming Growth Factor alpha; Transforming Growth Factor beta; Wound Healing

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant corneal stromal dystrophy that is caused by p.Arg124His mutation of transforming growth factor β induced (TGFBI) gene. It is characterized by well demarcated granular shaped opacities in central anterior stroma and as the disease progresses, extrusion of the deposits results in ocular pain due to corneal epithelial erosion. Also, diffuse corneal haze which appears late, causes decrease in visual acuity. The prevalence of GCD2 is high in East Asia including Korea. Homozygous patients show a severe phenotype from an early age, and the heterozygote phenotype varies among patients, depending on several types of compound heterozygous TGFBI mutations. In the initial stage, conservative treatments such as artificial tears, antibiotic eye drops, and bandage contact lenses are used to treat corneal erosion. Different surgical methods are used depending on the depth and extent of the stromal deposits. Phototherapeutic keratectomy removes anterior opacities and is advantageous in terms of its applicability and repeatability. For deeper lesions, deep anterior lamellar keratoplasty can be used as the endothelial layer is not always affected. Recurrence following these treatments are reported within a wide range of rates in different studies due to varying definition of recurrence and follow-up period. In patients who have undergone corneal laser vision-correction surgeries such as photorefractive keratectomy, LASEK, or LASIK including SMILE surgery, corneal opacity exacerbates rapidly with severe deterioration of visual acuity. Further investigations on new treatments of GCD2 are necessary.

Topics: Cornea; Corneal Dystrophies, Hereditary; Corneal Opacity; Corneal Ulcer; Humans; Keratomileusis, Laser In Situ; Photorefractive Keratectomy; Transforming Growth Factor beta

Platelet-rich plasma (PRP) harbors high concentrations of growth factors related to the promotion of wound healing. We evaluated the efficacy of PRP eyedrops in the treatment of persistent epithelial defects (PEDs).. Autologous PRP and autologous serum (AS) were prepared from whole blood. The concentrations of transforming growth factor (TGF)-β1, TGF-β2, epidermal growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed and compared. The corneal epithelial healing efficacy of PRP was compared with that of AS in patients with PED induced by post-infectious inflammation.. The concentrations of TGF-β1, TGF-β2, EGF, vitamin A and fibronectin in the PRP and AS were not statistically different. However, the concentrations of EGF in the PRP were significantly greater than in the AS. AS was used in 17 and PRP in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP-treated eyes were significantly higher than those treated with AS.. The PRP was effective in the treatment of PEDs. This may be attributable to its high concentration of platelet-contained growth factors, most notably EGF. PRP could be an effective, novel treatment option for chronic ocular surface disease.

Topics: Adult; Aged; Aged, 80 and over; Cell Proliferation; Chromatography, High Pressure Liquid; Corneal Diseases; Corneal Ulcer; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Epithelium, Corneal; Eye Infections, Bacterial; Female; Fibronectins; Humans; Male; Middle Aged; Ophthalmic Solutions; Platelet Count; Platelet-Rich Plasma; Retrospective Studies; Serum; Transforming Growth Factor beta; Vitamin A; Wound Healing

We investigated the wound healing effect of retinyl palmitate eyedrops following a corneal alkali burn in rats.. A total of 160 Sprague-Dawley male rats were divided into two groups and central corneas were injured by contacting eyes with filter paper saturated with 0.01 m NaOH for 45 seconds. Vitamin A group was treated with retinyl palmitate and antibiotic (Cravit(®) : 0.5% levofloxacin) eye drops four times daily for 3 days and the control group with vehicle and antibiotic eye drops. Corneal wound healing by fluorescein staining and impression cytologic analysis were conducted at 0, 24, 48 and 72 hr after injury. Vascular endothelial growth factor A (VEGF-A), thrombospondin 2, matrix metalloproteinase 9 (MMP 9) and transforming growth factor-β (TGF-β) were measured in corneas by ELISA, immunofluorescent staining and real-time PCR.. Corneal wound healing was better in the vitamin A group than in the control group. Early sprouting of new vessel was observed in the control group at 72 hr, but not in the vitamin A group. Corneal thrombospondin 2 proteins in ELISA were higher in the vitamin A group, but VEGF-A, MMP 9 and TGF-β proteins were higher in the control group (p < 0.05). Similarly, thrombospondin 2 immunofluorescent staining was stronger, whereas VEGF-A, MMP 9 and TGF-β staining were weaker in the vitamin A group (p < 0.05). In addition, thrombospondin 2 mRNA levels were higher, whereas VEGF-A, MMP 9 and TGF-β mRNA levels were lower in the vitamin A group (p < 0.05).. Retinyl palmitate eye drops can inhibit VEGF-A and activate thrombospondin 2 and improve conjunctival impression cytologic findings. Furthermore, retinyl palmitate eye drops were found to promote corneal healing after an alkali burn in rats.

Topics: Animals; Burns, Chemical; Corneal Ulcer; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eye Burns; Fluorescent Antibody Technique, Indirect; Male; Matrix Metalloproteinase 9; Ophthalmic Solutions; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger; Sodium Hydroxide; Thrombospondins; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vitamin A; Vitamins; Wound Healing

Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confocal microscopy, zymography, immunoblots, and real-time polymerase chain reaction. In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelio-stromal boundary. The role of epithelial-stromal interaction in MMP induction was investigated in an in vitro co-culture system and demonstrated an induction and co-localization of EMMPRIN and MMP-2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN-containing purified epithelial cell membranes also induced MMP-1, MMP-2, and EMMPRIN and this was inhibited by a blocking anti-EMMPRIN antibody, suggesting that EMMPRIN was primarily responsible for this induction. These findings, and the up-regulation of EMMPRIN by epidermal growth factor and transforming growth factor-beta, demonstrate a role for EMMPRIN in wound healing and suggest that sustained local up-regulation of EMMPRIN and MMPs in chronic situations in which healing is delayed may lead to excessive matrix degradation and corneal melts.

Topics: Antigens, CD; Antigens, Neoplasm; Basigin; Cell Line; Cholera Toxin; Coculture Techniques; Cornea; Corneal Ulcer; DNA Primers; Epidermal Growth Factor; Epithelium, Corneal; Fibroblasts; Humans; Immunohistochemistry; Insulin; Microscopy, Confocal; Polymerase Chain Reaction; Reference Values; Transforming Growth Factor beta; Transforming Growth Factor beta1

Topics: Cicatrix; Collagen; Corneal Opacity; Corneal Ulcer; Epithelium, Corneal; Humans; Lasers, Excimer; Myopia; Photorefractive Keratectomy; Recurrence; Transforming Growth Factor beta