Paraneoplastic ocular sarcoid-like reaction in the setting of pulmonary sarcoid-like reaction and lung adenocarcinoma: A case report and literature review.

Purpose: To describe ocular sarcoid-like reaction as a unique manifestation of paraneoplastic syndrome in the context of concurrent pulmonary sarcoid-like reaction and lung adenocarcinoma. Methods: Single case report and narrative review. Results: A 59-year-old male patient presented with a year-long history of diminished vision and weight loss. Clinical examination revealed panuveitis and multiple chorioretinal lesions. A CT scan of the chest revealed mediastinal and hilar lymphadenopathy as well as a spiculated right lower lung nodule concerning for malignancy. Subsequent bronchoscopy and biopsy confirmed lung adenocarcinoma and non-caseating granulomas in sentinel lymph nodes. Conclusion: Although pulmonary granulomatous reaction can be seen in the setting of lung malignancy, and ocular sarcoid-like reaction may present as a paraneoplastic manifestation of systemic malignancy, the presence of concomitant pulmonary and ocular sarcoid-like reactions distinguishes this case. The findings underscore the importance of a systemic workup for patients with concerning constitutional symptoms, as paraneoplastic syndromes and metastatic diseases may mimic uveitis. Recognition of paraneoplastic sarcoidosis as a potential clinical manifestation is essential, especially in patients with chronic illness indicators, necessitating a comprehensive evaluation for malignancy.

Nanoparticle-based targeting of microglia improves the neural regeneration enhancing effects of immunosuppression in the zebrafish retina.

Retinal Müller glia function as injury-induced stem-like cells in zebrafish but not mammals. However, insights gleaned from zebrafish have been applied to stimulate nascent regenerative responses in the mammalian retina. For instance, microglia/macrophages regulate Müller glia stem cell activity in the chick, zebrafish, and mouse. We previously showed that post-injury immunosuppression by the glucocorticoid dexamethasone accelerated retinal regeneration kinetics in zebrafish. Similarly, microglia ablation enhances regenerative outcomes in the mouse retina. Targeted immunomodulation of microglia reactivity may therefore enhance the regenerative potential of Müller glia for therapeutic purposes. Here, we investigated potential mechanisms by which post-injury dexamethasone accelerates retinal regeneration kinetics, and the effects of dendrimer-based targeting of dexamethasone to reactive microglia. Intravital time-lapse imaging revealed that post-injury dexamethasone inhibited microglia reactivity. The dendrimer-conjugated formulation: (1) decreased dexamethasone-associated systemic toxicity, (2) targeted dexamethasone to reactive microglia, and (3) improved the regeneration enhancing effects of immunosuppression by increasing stem/progenitor proliferation rates. Lastly, we show that the gene rnf2 is required for the enhanced regeneration effect of D-Dex. These data support the use of dendrimer-based targeting of reactive immune cells to reduce toxicity and enhance the regeneration promoting effects of immunosuppressants in the retina.