RESUMO
We report a case of multifocal choroidal melanoma in the same eye, separated in presentation by 20 years. A 57-year-old Caucasian male initially presented with a choroidal melanoma of the right eye that was treated with transpupillary thermotherapy. Due to recurrence, the patient underwent proton beam therapy with subsequent tumor regression. A second small choroidal lesion was noted in the right eye during his surveillance examinations that was closely monitored and demonstrated stable dimensions and features suggestive of a choroidal nevus. Twenty years after his first presentation, the second lesion exhibited accelerated growth with imaging studies indicative of transformation to a distinct choroidal melanoma. The patient underwent a second globe salvage treatment of proton beam therapy. We describe the clinical course, radiographic, and imaging findings of this rare choroidal melanoma.
RESUMO
A systems pharmacological approach that capitalizes on the characterization of intracellular signaling networks can transform our understanding of human diseases and lead to therapy development. Here, we applied this strategy to identify pharmacological targets for the treatment of Stargardt disease, a severe juvenile form of macular degeneration. Diverse GPCRs have previously been implicated in neuronal cell survival, and crosstalk between GPCR signaling pathways represents an unexplored avenue for pharmacological intervention. We focused on this receptor family for potential therapeutic interventions in macular disease. Complete transcriptomes of mouse and human samples were analyzed to assess the expression of GPCRs in the retina. Focusing on adrenergic (AR) and serotonin (5-HT) receptors, we found that adrenoceptor α 2C (Adra2c) and serotonin receptor 2a (Htr2a) were the most highly expressed. Using a mouse model of Stargardt disease, we found that pharmacological interventions that targeted both GPCR signaling pathways and adenylate cyclases (ACs) improved photoreceptor cell survival, preserved photoreceptor function, and attenuated the accumulation of pathological fluorescent deposits in the retina. These findings demonstrate a strategy for the identification of new drug candidates and FDA-approved drugs for the treatment of monogenic and complex diseases.