Drosophila mTOR complex2 preserves mitochondrial and cardiac function under high fat diet treatment

High fat diet (HFD)-associated lipotoxicity is one of the major causes of cardiovascular diseases. The mechanistic target of rapamycin (mTOR) pathway, especially mTOR complex 1 (mTORC1), has been previously implicated in HFD-induced heart dysfunction. In the present study, we find that unlike mTORC1, mTOR complex 2 (mTORC2) protects hearts from HFD-induced cardiomyopathy and mitochondrial dysfunction in Drosophila. We show that HFD feeding induces contractile dysfunction along with altered mitochondrial morphology and function. Upon HFD feeding, the mitochondria of cardiomyocytes exhibit fragmentation, loss of membrane potential, and calcium overload. Interestingly, HFD feeding also reduces the activity of cardiac mTORC2. In line with this finding, the flies with cardiac-specific knockdown of rictor, the key subunit of mTORC2, show cardiac and mitochondrial dysfunction similar to what is observed in HFD-fed wild-type flies. Conversely, cardiac-specific activation of mTORC2 by overexpressing rictor attenuates HFD-induced mitochondrial and cardiac dysfunction. Thus, our findings suggest that mTORC2 is a cardioprotective factor and regulates mitochondrial homeostasis upon HFD feeding.This is a preprint made available through bioRxiv at doi:https://doi.org/10.1101/2021.01.27.428443

Histocompatibility Leukocyte Antigen-A29-Associated Retinal Vasculitis without Choroidal Lesions: A Report of 4 Cases

This study describes a cohort of patients presenting with histocompatibility leukocyte antigen (HLA)-A29-associated retinal vasculitis without choroidal lesions that may share clinical features with birdshot retinochoroiditis. The methods include a retrospective chart review of patients presenting with HLA-A29-associated retinal vasculitis without choroidal lesions. The data on the patients were entered retrospectively into a new database and analyzed. Four patients who had HLA-A29-associated retinal vasculitis without choroidal lesions were identified. The median age at presentation was 40 years (range: 14–71); 75% were female. At presentation, all four patients had a visual acuity of 20/50 or better in both eyes. All the eyes had mild vitritis, three eyes (37.5%) had cystoid macular edema, and two eyes (25%) had optic disc edema. All the patients required treatment with systemic steroids and immunosuppressive therapy. HLA-A29-associated retinal vasculitis without choroidal lesions appears to share many clinical features with birdshot chorioretinitis, including the need for systemic immunosuppressive therapy. Whether this entity represents an early form of birdshot retinochoroiditis or a more localized variant of the disease is a topic for additional studies