Molecular Retinal Changes Accompanying Hormonal Chemotherapy Treatment

Abstract

The increased use of chemotherapeutic agents has resulted in longer cancer patient survival. Consequently the ophthalmologist is seeing more patients with adverse ocular side effects secondary to these antineoplastic agents. Systemic anti-cancer therapies can produce acute and chronic organ damage. Bone marrow suppression, hepatic, pulmonary, cardiac, renal and gastrointestinal toxicities of chemotherapeutic agents used in treating cancer patients are well known. The development of more aggressive regimens as well as newer agents and combination chemotherapies have resulted in significant increase of reported cases of chemotherapy induced ocular side effects. Ocular toxicity induced by cancer chemotherapy includes a broad spectrum of disorders, reflecting the unique anatomical, physiological and biochemical features of the eye. Understanding the ocular side effects will assist the ophthalmologist and oncologist to recognize them early and intervene before blindness occurs. Anticancer agents are classified into several broad groups, which are usually defined according to their different mechanisms of action. Most chemotherapeutic agents have the capacity to induce, either directly or indirectly, potentially lethal damages to tumor cells. Hormone therapy is one type of chemotherapy (systemic therapy) and it is used to treat tumors which are hormone dependent or which need sex hormones to grow. Tamoxifen is a selective estrogen receptor modulator (SERM) and acts against breast cancer by occupying estrogen receptors. It’s the only SERM approved for every stage of breast cancer. It interferes with the binding of estradiol to its target tissues by depletion of cytoplasmic receptors and competitive inhibition at the receptor site. Because estrogen affects a XV wide variety of physiological functions and estrogen receptors are present in the eye, the changes in estrogenic activity brought about by tamoxifen have the potential to affect visual processing. The aim of this study was undertaken to estimate the incidence of retinal changes associated with prolonged administration of 5,10 and 15 mg/kg of tamoxifen treatment up to 6 months. Anticipation of various treatment related toxicities may also provide the opportunity to develop intervention strategies that could minimize expected adverse effects and understand the causation of tamoxifen ocular toxicity in particular its molecular structure retinal changes. Sixty healthy New Zealand white rabbits of either sex, weighing 2-2.5 Kg were divided into 4 main groups: Control group: (n = 15) kept untreated as a normal group and the others three groups were administrated tamoxifen orally through the stomach tube once daily with doses 5, 10 and 15 mg/kg. Rabbits groups were subdivided into three subgroups and