# Diabetic Retinopathy and Ocular Melanoma: How Far We Are? [PERSON]  
1 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; [EMAIL_ADDRESS] (J.R.C. ); [EMAIL_ADDRESS] (R.D.A. ); [EMAIL_ADDRESS] (J.F.F.) [PERSON]  
1 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; [EMAIL_ADDRESS] (J.R.C. ); [EMAIL_ADDRESS] (R.D.A. ); [EMAIL_ADDRESS] (J.F.F.) [PERSON]  
1 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; [EMAIL_ADDRESS] (J.R.C. ); [EMAIL_ADDRESS] (R.D.A. ); [EMAIL_ADDRESS] (J.F.F.) [PERSON]. [PERSON]. vision [2; 3]. Internal and external retinal blood barriers (BRB) preserve the retina and, under ideal physiological conditions, regulate the flow of ions, proteins and water [3]. Diabetic retinopathy (DR) causes vision loss, which is the predominant cause of blindness in the population worldwide. Retinal neovascularization and oxidative stress (due to the hyperglycaemic environment) are the most common features found in this disorder [4; 5]. In addition, there are also several factors (e.g., inflammation) leading to the break of both internal and external BRB and causing the progression of macular edema, which is the predominant cause of vision loss in diabetic patients. In this scenario, the cells that make up the external BRB--retinal pigmented epithelial cells (RPE)--are under hyperosmolar stress [3]. The breaking of BRB results in the increase of retinal osmotic pressure and accumulation of water, with increased risk of developing macular edema and impaired vision. RPE cells are thus subjected both to hyperosmolar stress (HOS) in the apical membrane and to hyperosmolar stimulus by enhanced plasma osmolarity [6; 7]. In this context, glucose induces hyperosmolarity and causes angiogenesis and retinopathy by activating the transcription factor tonicity-responsive binding-protein (TonEBP)/nuclear factor of activated T-cells [7]. Recent studies have also proposed that increased age-related plasma osmolarity intensifies age-related macular degeneration (AMD) through the promotion of inflammation and retinal angiogenesis [8]. It is well known that AMD and choroidal neovascularization (CNV) are strongly linked to DR, as the onset of one disease can lead to the other. All these diseases are thus associated with each other. [PERSON] et al. reported that subclinical macular edema, found in 54% of uveal melanoma patients, increased the tumour thickness and diameter [9]. It has also been shown that the events causing new and abnormal blood vessels (angiogenesis or neovascularization and vasculogenesis) related to the differentiation of circulating bone-marrow-derived endothelial precursor cells are also present in uveal melanoma [10; 11]. The relationship between retinopathy and ocular melanoma is well documented [12; 13]. Melanoma is a primary tumour mostly affecting the eyes in adulthood, with an annual worldwide prevalence of 5.5 to 10.9 cases per million people [14]. Melanomas are classified as cutaneous and non-cutaneous. Only 5% of melanomas affect the ocular region, and these can develop in the conjunctiva, eyelid or orbit [15]. Out of the ocular melanomas, only 5% affect the conjunctiva, while the remaining 95% affect the intraocular structure of the eye and arise from the uvea (i.e., iris, ciliary body and choroid). As its name suggests, melanoma is derived from melanocytes and usually develops metastases (mainly in the liver). People with clear skin and blue eyes, together with cutaneous nevi, congenital ocular melanocytosis, uveal melanocytoma and neurofibromatosisis account for the major risk factors of melanoma.