Introduction: To investigate the effect of high myopia on the expression of retinal osteopontin (OPN) and integrin αVβ 3 receptor in guinea pigs and determined the relationship between high myopia and diabetic retinopathy. Methods: Ninety 3-week-old male guinea pigs were randomly divided into four groups that included normal control group (NOR，n=18), high myopia group (HM，n=24), diabetes group (DR，n=24), and diabetes with high myopia group (DR+HM，n=24). HM was induced by form deprivation (FDHM) in the right eye. The DR group was injected with 5% streptozotocin(STZ) 280 mg/kg intraperitoneally in the lower left abdomen of guinea pigs. The DRHM group was subjected to the same treatment as the HM and DR groups. Eighteen guinea pigs in each group were randomly selected to complete the experimental measurement. After enucleation of eyeballs, HE and immunohistochemical staining were performed to observe the retina morphology and count the positive rate of OPN and integrin αvβ 3 receptor. Results: Diabetic retinal changes were found in group DR and HM+DR. The degree of retinal change in group HM+DR was less than that in group DR. In the DR group, the morphology of retinal tissue was loose, the number of cells decreased, increased retinal microaneurysms, and a small amount of small artery embolism and venous thrombosis were observed. Although the retinal structure in the HM+DR group also became thinner, looser, and disordered, only a small number of microaneurysms were observed compared with the diabetic group. Immunohistochemical staining showed that the expression of OPN and integrin αvβ 3 receptors in the diabetic groups (DR, HM+DR) was significantly higher than in the HM and NOR groups. The positive expression rates of OPN and integrin αvβ 3 receptors in group HM+DR were significantly lower than those in group DR (P

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