Maküler kornea distrofisinin mikroakışkan platform içerisinde in vitro hastalık modellenmesi

Cornea is an avascular structure that provides refraction, transparency, and protects the eye's anterior part. Collagen generates a unique tissue structure that promotes physical qualities and strengthens the rigidity of the outer eye. Corneal dystrophies are rare hereditary diseases that produce corneal defects. Macular corneal dystrophy (MCD) is an autosomal recessively inherited condition in which mutations in the CHST6 gene, which codes for the enzyme N-acetylglucosamine-6-sulfotransferase, induce aberrant proteoglycan production. Corneal opacity is caused by the accumulation of glycosaminoglycans among stroma keratocytes, resulting in visual impairment. MMP1 and MMP13 from the matrix metalloproteinase (MMP) family, which are involved in corneal remodeling, have been found to be reduced in the extracellular matrix in MCD disease. Current clinical methods are mostly focused on corneal transplants, which do not eliminate the risk of recurrence. Here, we create a dynamic microfluidic platform to test an alternate treatment technique that includes MMP enzyme therapy in an in vitro model of MCD. Primary human corneal cells were extracted and planted on a hydrogel made up of mainly collagen which mimicked the biochemical and mechanical properties of the cornea. The cells were cultivated in a microfluidic platform in continuous laminar flow under dynamic conditions. We demonstrate that imitating sulfation inhibition using sodium chlorate, a pharmacological inhibitor of 3′-phosphoadenosine-5′-phosphosulfate (PAPs), results in long-term cell survival and MCD (-) related molecular responses at the gene level. The bioengineered example disease model will be a good platform for learning more about MCD and creating new treatments in clinics. Key Words: Microfluidics, Disease Modelling, Rare Disease, Macular Corneal Dystrophy