A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea.
The corneal fibrotic responses to corneal damage often lead to severe corneal opacification thereby resulting in severe visual impairment or even blindness. The persistence of corneal opacity depends heavily on the activity of corneal myofibroblast. Myofibroblasts are opaque and synthesize a disorganized extracellular matrix (ECM) and thus promoting opacification. Cluster of differentiation 147 (CD147), a member of the immunoglobulin superfamily, is known to play important roles in the differentiation process from fibroblast to myofibroblast in damaged cornea and may therefore be an effective target for treatment of corneal opacity. Here, we examined the therapeutic efficacy of novel CD147 inhibiting verbenone derivative SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) on corneal fibrosis. Topical SP-8356 significantly reduced corneal haze and fibrosis in the alkali-burned cornea. In detail, SP-8356 inhibited both alpha-smooth muscle actin (α-SMA) expressing myofibroblast and its ECM-related products, such as matrix-metalloproteinase-9 and collagen type III and IV. Similar to SP-8356, topical corticosteroid (prednisolone acetate, PA) also reduced the ECM-related products and opacification. However, prednisolone acetate failed to decrease the population of α-SMA-positive corneal myofibroblast. In conclusion, SP-8356 is capable enough to prevent corneal haze by preventing pathological fibrosis after severe corneal damage. Therefore, SP-8356 could be a potentially promising therapeutic drug for corneal fibrosis.
['Joung|Chanmin|C|', 'Noh|Hyojin|H|', 'Jung|Jeein|J|', 'Song|Hwa Young|HY|', 'Bae|Hwanse|H|', 'Pahk|Kisoo|K|0000-0003-2971-4202', 'Kim|Won-Ki|WK|']
D000468:Alkalies D000818:Animals D051926:Basigin D000081008:Bicyclic Monoterpenes D001706:Biopsy D003094:Collagen D065306:Corneal Injuries D016207:Cytokines D004195:Disease Models, Animal D005126:Eye Burns D005347:Fibroblasts D005355:Fibrosis D007150:Immunohistochemistry D018836:Inflammation Mediators D008297:Male D051381:Rats
myofibroblast corneal haze alpha-smooth muscle actin collagen type III MMP-9 corneal alkali burn matrix-metalloproteinase