Application of clotrimazole via a novel controlled release device provides potent retinal protection.

Zhaleh Kashkouli Nezhad,Toru Nakazawa,Toshiaki Abe,Hideyuki Saya,Nobuhiro Nagai,Hirokazu Kaji,Matsuhiko Nishizawa,Kotaro Yamamoto

doi:10.1007/s10856-015-5561-9

Zhaleh Kashkouli Nezhad, Toru Nakazawa + Show 6 more

Open Access

https://doi.org/10.1007/s10856-015-5561-9

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Abstract

Age-related macular degeneration is the leading cause of legal blindness among older individuals. Therefore, the development of new therapeutic agents and optimum drug delivery systems for its treatment are crucial. In this study, we investigate whether clotrimazole (CLT) is capable of protecting retinal cells against oxidative-induced injury and the possible inhibitory effect of a sustained CLT-release device against light-induced retinal damage in rats. In vitro results indicated pretreatment of immortalized retinal pigment epithelium cells (RPE-J cells) with 10–50 µM CLT before exposure to oxygen/glucose deprivation conditions for 48 h decreased the extent of cell death, attenuated the percentage of reactive oxygen species-positive cells, and decreased the levels of cleaved caspase-3. The device consists of a separately fabricated reservoir, a CLT formulation, and a controlled release cover, which are made of poly(ethyleneglycol) dimethacrylate (PEGDM) and tri(ethyleneglycol) dimethacrylate (TEGDM). The release rate of CLT was successfully tuned by changing the ratio of PEGDM/TEGDM in the cover. In vivo results showed that use of a CLT-loaded device lessened the reduction of electroretinographic amplitudes after light exposure. These findings indicate that the application of a polymeric CLT-loaded device may be a promising method for the treatment of some retinal disorders.

Highlights

Age-related macular degeneration (AMD) occurs primarily in elderly people and is the leading cause of legal blindness among older individuals in the developed world [1,2,3] It has been predicted that as the population ages, there will be a 50 % increase in the incidence of AMD before 2020 [4]
To investigate whether CLT could protect retinal pigment epithelium (RPE)-J cells against oxidative stress, and to clarify the effective doses of CLT, cells were pretreated with CLT and cultured under OGD conditions
The data confirmed that CLT-pretreated RPE-J cells showed significantly better cell survival under OGD conditions compared to non-pretreated cells and the increase in this viability was CLT-dose-dependent, i.e. administration of 10 lM showed the highest protection (Fig. 1)

Summary

Introduction

Age-related macular degeneration (AMD) occurs primarily in elderly people and is the leading cause of legal blindness among older individuals in the developed world [1,2,3] It has been predicted that as the population ages, there will be a 50 % increase in the incidence of AMD before 2020 [4]. AMD derives from pathologic alterations of retinal pigment epithelium (RPE) cells as well as its related tissues and their interactions with the local environment [5]. J Mater Sci: Mater Med (2015) 26:230 one of the major ocular tissues affected by oxidative stress and is known to play an important role in pathogenesis of AMD [7]. The protection of RPE cells against oxidative damage may be important in retinal protection for the treatment of AMD [8]. The molecular size and physical characteristics of the substance affect its topical delivery [11]. Transscleral delivery is potentially a more applicable method for drug delivery to the posterior segment of the eye compared to topical application [14]

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