Sean Tighe1, Hamid-Reza Moein2, Lorraine Chua3, Anny Cheng4, Pedram Hamrah2, Scheffer C G Tseng5. 1. TissueTech, Inc., Miami, Florida, United States 2Florida International University, Herbert Wertheim College of Medicine, Miami, Florida, United States. 2. Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States. 3. TissueTech, Inc., Miami, Florida, United States. 4. TissueTech, Inc., Miami, Florida, United States 2Florida International University, Herbert Wertheim College of Medicine, Miami, Florida, United States 4Ocular Surface Center and Ocular Surface Research & Education Foundation, Miami, Florida, United States. 5. TissueTech, Inc., Miami, Florida, United States 4Ocular Surface Center and Ocular Surface Research & Education Foundation, Miami, Florida, United States.
Abstract
Purpose: To evaluate morselized amniotic membrane and umbilical cord (AMUC) eye drops in promoting corneal re-epithelialization. Methods: Following a 2-mm diameter central epithelial wound in one eye of 48 normal C57BL/6 mouse corneas, 10 μL of saline with (n = 24) or without (n = 24) AMUC was applied three times a day for 6 days. The corneal epithelial defect was measured using 0.1% fluorescein, while corneal epithelial regularity was measured by assessment of a reflected light off the corneal surface. Hematoxylin and eosin and immunohistochemistry was performed for Ki-67, CD45, βIII-tubulin, and keratin12. Safety and toxicity were also assessed by monitoring physical activity and body weight. Results: Compared with the vehicle saline control, AMUC resulted in a significantly smaller corneal epithelial defect at 12 hours (P = 0.002), 1 day (P = 0.016), and 2 days (P = 0.04) post abrasion. Amniotic membrane and umbilical cord also achieved a more rapid complete epithelialization (3.15 ± 1.44 vs. 4.00 ± 1.63 days, P = 0.06) and induced a higher incidence of corneal regularity without affecting physical activity and body weight. Spearman correlation showed that epithelialization was significantly correlated with treatment groups (P < 0.001), time (P < 0.001), and corneal regularity (P = 0.04). Amniotic membrane and umbilical cord significantly decreased CD45+ cell infiltration in the peripheral cornea (P < 0.05) and promoted Ki-67+ cells in the central corneal epithelium (P < 0.05). Conclusion: Topical AMUC significantly promotes corneal epithelialization and restores corneal regularity by reducing inflammation and promoting proliferation in a murine model of corneal abrasion without causing safety or toxicity concerns. This encouraging preclinical finding warrants a controlled human trial in the future.
Purpose: To evaluate morselized amniotic membrane and umbilical cord (AMUC) eye drops in promoting corneal re-epithelialization. Methods: Following a 2-mm diameter central epithelial wound in one eye of 48 normal C57BL/6 mouse corneas, 10 μL of saline with (n = 24) or without (n = 24) AMUC was applied three times a day for 6 days. The corneal epithelial defect was measured using 0.1% fluorescein, while corneal epithelial regularity was measured by assessment of a reflected light off the corneal surface. Hematoxylin and eosin and immunohistochemistry was performed for Ki-67, CD45, βIII-tubulin, and keratin12. Safety and toxicity were also assessed by monitoring physical activity and body weight. Results: Compared with the vehicle saline control, AMUC resulted in a significantly smaller corneal epithelial defect at 12 hours (P = 0.002), 1 day (P = 0.016), and 2 days (P = 0.04) post abrasion. Amniotic membrane and umbilical cord also achieved a more rapid complete epithelialization (3.15 ± 1.44 vs. 4.00 ± 1.63 days, P = 0.06) and induced a higher incidence of corneal regularity without affecting physical activity and body weight. Spearman correlation showed that epithelialization was significantly correlated with treatment groups (P < 0.001), time (P < 0.001), and corneal regularity (P = 0.04). Amniotic membrane and umbilical cord significantly decreased CD45+ cell infiltration in the peripheral cornea (P < 0.05) and promoted Ki-67+ cells in the central corneal epithelium (P < 0.05). Conclusion: Topical AMUC significantly promotes corneal epithelialization and restores corneal regularity by reducing inflammation and promoting proliferation in a murine model of corneal abrasion without causing safety or toxicity concerns. This encouraging preclinical finding warrants a controlled human trial in the future.
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