Effects of Curcumin on Epidermal Growth Factor in Proliferative Vitreoretinopathy

Abstract

Background/Aims: Proliferative vitreoretinopathy (PVR) is a common refractory eye disease that causes blindness and occurs after retinal detachment or retinal reattachment. Epidermal growth factor (EGF) has been shown to play an important role in the migration and proliferation of retinal pigment epithelium (RPE) cells, which promote PVR. Curcumin inhibits RPE cell proliferation, but it is not known whether it participates in the formation of PVR. Curcumin regulates the biological functions of EGF, which plays important roles in the development of PVR. This study aimed to evaluate the effect of curcumin on the regulation of EGF in PVR. Methods: Rabbit RPE cells were cultured, and EGF expression was detected by immunocytochemistry. MTT assay was conducted to determine cell proliferation induced by different concentrations of EGF. Immunocytochemical staining was used to detect EGF expression after treatment with curcumin at varying concentrations. Real-time PCR (RT-PCR) and western blot analysis were used to detect the concentrations of EGF mRNA and protein after treatment with curcumin. After RPE cells and curcumin were injected into experimental rabbit eyes, the cornea, aqueous humor, lens, and vitreous opacity were observed and recorded simultaneously by indirect ophthalmoscopy, fundus color photography, and B-ultrasonography. The vitreous body was extracted, and the EGF content in the vitreous humor was measured by enzyme-linked immunosorbent assay (ELISA). Results: At each time point (24, 48, and 72 h), cell proliferation gradually increased with increasing EGF concentrations (0, 3, 6, and 9 ng/mL) in a dose-dependent manner. Cell proliferation between EGF concentrations of 9 and 12 ng/mL were no different, which suggested that 9 ng/mL EGF was the best concentration to use to stimulate RPE cell proliferation in vitro. Under all EGF concentrations (0, 3, 6, 9, and 12 ng/mL), RPE cell proliferation increased with time (from 24 to 72 h), suggesting a time–effect relationship. Curcumin downregulated EGF expression in RPE cells, which also indicated time–effect and dose–effect relationships. The best curcumin concentration for the inhibition of EGF expression was 15 µg/mL. RT-PCR and western blot analyses indicated that the EGF mRNA and expression of the protein in RPE cells treated with curcumin significantly decreased with time. Ocular examinations revealed that the vitreous opacity was lower and the proliferative membrane was thinner in the curcumin group compared with the control group. The PVR grade and the incidence of retinal detachment were significantly lower in the experimental group than in the control group. ELISA results showed that the EGF content in vitreous humor was higher in the control group than in the curcumin group. The curcumin and control groups were significantly different at each time point. Conclusion: Curcumin inhibited RPE cell proliferation by downregulating EGF and thus effectively inhibited the initiation and development of PVR.

Role of Curcumin in Retinal Diseases—A review

“…EGF protein expression in RPE cells by western blot analysis in the curcumin group decreased with time. Vitreous clouding seen by slit-lamp biomicroscopy and indirect ophthalmoscopy reduced in the curcumin group on day 7 and PVR membrane, which was graded using colour fundus photography, ultrasound B scan and indirect ophthalmoscopy, showed lower grading, being thin and lower incidence of retinal detachment (11% vs 61%, 16% vs 75% and 16% vs 83%) on days 14, 21 and 28 post-treatment with curcumin [ 64 ]. Retinal Ischemia–Reperfusion Injury (RIRI) This happens due to ocular hypertension or as a consequence of stroke in hypertension.…”

Systemic Curcumin-Human Serum Albumin in Proliferative Vitreoretinal Retinopathy: A Pilot Study

“…Curcumin would therefore be a promising approach as it has several promising effects on PVR prevention and treatment [ 18 ]. It reverses epithelial-to-mesenchymal transition (EMT) [ 19 ], inhibits RPE cell proliferation [ 20 ], promotes human RPE cell death through organized apoptotic pathways [ 21 ], and induces cell cycle arrest by activating multiple checkpoints [ 22 ]. Thus, pathological cell growth triggered by growth factors through stress and inflammation can be suppressed.…”

Anti‑inflammatory role of curcumin in retinal disorders (Review)

“…It can be defined as a form of wound healing process induced by the epidermal growth factor and mainly characterized by RPE cell proliferation and migration. Ren et al (52) described a significant reduction of RPE cell proliferation and of vitreous opacity in the group of patients who received curcumin in comparison with the control group.…”