Collagen peptide modified carboxymethyl cellulose as both antioxidant drug and carrier for drug delivery against retinal ischaemia/reperfusion injury.

Hua Mu,Yue Xing,Haiying Wei,Haijing Wang,Zhuolei Feng,Hong Lu,Yeqing Wang,Hongmin Yu

doi:10.1111/jcmm.13768

Abstract

Oxidative stress can cause injury in retinal endothelial cells. Carboxymethyl cellulose modified with collagen peptide (CMCC) is of a distinct antioxidant capacity and potentially a good drug carrier. In this study, the protective effects of CMCC against H2O2‐induced injury of primary retinal endothelial cells were investigated. In vitro, we demonstrated that CMCC significantly promoted viability of H2O2‐treated cells, efficiently restrained cellular reactive oxygen species (ROS) production and cell apoptosis. Then, the CMCC was employed as both drug and anti‐inflammatory drug carrier for treatment of retinal ischaemia/reperfusion (I/R) in rats. Animals were treated with CMCC or interleukin‐10‐loaded CMCC (IL‐10@CMCC), respectively. In comparisons, the IL‐10@CMCC treatment exhibited superior therapeutic effects, including better restoration of retinal structural thickness and less retinal apoptosis. Also, chemiluminescence demonstrated that transplantation of IL‐10@CMCC markedly reduced the retinal oxidative stress level compared with CMCC alone and potently recovered the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that CMCC provides a promising platform to enhance the drug‐based therapy for I/R‐related retinal injury.

Highlights

Retinal ischaemia/reperfusion (I/R) injury was one of important factors responsible for the pathogenesis of multiple ocular diseases, including diabetic retinopathy, acute glaucoma and retinopathy of prematurity.[1,2] retinal I/R injury developed vision loss and even blindness, owing to eternal damage to the retina, retinal neurons.[3,4,5] Ischaemia blocked blood flow to retina, causing the transient deficiency of oxygen and other physiological nutrients, such as adenosine triphosphate.[6]
The following quantification results of transferase UTP nick end labelling (TUNEL) by flow cytometry (Figure 3A) clearly indicated that apoptosis in the control group was significantly lower than H2O2‐treated group and this change could be considerably ameliorated by supplementing antioxidative gels
The accumulation of intracellular reactive oxygen species (ROS) could inhibit the Akt‐signal pathway,[38] followed by down‐regulating survival signals, including Bcl‐2 and activating pro‐apoptotic factors, such as Bax and caspase 3 (Csp3).39 the high concentration of ROS was conducive to triggering the opening of the mitochondria permeability transition gates, leading to the release of apoptosis‐activating cytokines.[40]

Summary

| INTRODUCTION

Retinal ischaemia/reperfusion (I/R) injury was one of important factors responsible for the pathogenesis of multiple ocular diseases, including diabetic retinopathy, acute glaucoma and retinopathy of prematurity.[1,2] retinal I/R injury developed vision loss and even blindness, owing to eternal damage to the retina, retinal neurons.[3,4,5] Ischaemia blocked blood flow to retina, causing the transient deficiency of oxygen and other physiological nutrients, such as adenosine triphosphate.[6]. Carboxymethyl cellulose consisted of water‐soluble anionic polysaccharide and semisynthetic derivative of cellulose.[10] It possessed a broad range of practical applications, such as pharmaceuticals,[11] drug delivery[12] and wound dressing,[13] due to their high water content, biodegradability and biocompatibility. We preliminarily studied the underlying mechanism of enhanced restoration of retina from apoptosis with IL‐10‐loaded antioxidative gels by investigating the level of antioxidant enzyme and the mRNA expression of inflammatory cytokines

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION

| CONCLUSION