The myocardium/heart is the most mitochondria-rich tissue in the human body with mitochondria comprising approximately 30% of total cardiomyocyte volume. As the resident “powerhouse” of cells, mitochondria help to fuel the high energy demands of a continuously beating myocardium. It is no surprise that mitochondrial dysfunction underscores the pathogenesis of many cardiovascular ailments, including those of viral origin such as virus-induced myocarditis. Enteroviruses have been especially linked to injuries of the myocardium and its sequelae dilated cardiomyopathy for which no effective therapies currently exist. Intriguingly, recent mechanistic insights have demonstrated viral infections to directly damage mitochondria, impair the mitochondrial quality control processes of the cell, such as disrupting mitochondrial antiviral innate immune signaling, and promoting mitochondrial-dependent pathological inflammation of the infected myocardium. In this review, we briefly highlight recent insights on the virus-mitochondria crosstalk and discuss the therapeutic implications of targeting mitochondria to preserve heart function and ultimately combat viral myocarditis.

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. In the early stages of DR, the retina undergoes distinct epigenetic changes, including DNA methylation and histone modifications. Recent evidence supports unique epigenetic ‘signatures’ in patients with DR compared to non-diabetic controls. These DNA ‘signature’ sequences may be specific to the retina and may circulate in peripheral blood in the form of cell-free DNA (cfDNA). In this review, we explore the literature and clinical application of cfDNA sampling as an early, non-invasive, accessible assessment tool for early DR detection. First, we summarize the known epigenetic signatures of DR. Next, we review current sequencing technologies used for cfDNA detection, such as magnetic bead-based enrichment, next-generation sequencing, and bisulfite sequencing. Finally, we outline the current research limitations and emerging areas of study which aim to improve the clinical utility of cfDNA for DR evaluation.

Gene therapy represents a transformative frontier in ophthalmology, offering the potential to address inherited and acquired retinal diseases at their genetic origin rather than through symptomatic management. By introducing exogenous genetic material to restore or modulate gene expression, gene therapy aims to preserve or even restore vision in patients with mutations that disrupt normal retinal function. The eye’s small, compartmentalized structure, relative immune privilege, and direct accessibility through subretinal or intravitreal routes make it an ideal target for localized delivery with minimal systemic exposure. The approval of voretigene neparvovec-rzyl for RPE65-mediated retinal dystrophy marked a pivotal milestone, establishing proof of concept for durable and safe gene replacement therapy. Looking ahead, continued refinements in vector design, CRISPR-based editing strategies, and delivery platforms are expected to expand the therapeutic reach of gene therapy beyond monogenic disorders. With multiple early-phase clinical trials underway for inherited and acquired retinal diseases, the coming decade is poised to bring broader applicability, improved durability, and more accessible gene-based treatments across the spectrum of retinal pathology.

Diffuse intimal thickening (DIT) is a pre-clinical stage of atherosclerosis characterized by thickened intima. The molecular basis of its susceptibility to atherogenesis is unknown, and mechanistic investigations cannot be performed in commonly used mouse models, in which DIT does not exist. Vascular smooth muscle cells (SMCs) are the predominant cell type that occupies the intima and media of DIT. The molecular differences between these two layers may reveal the earliest phenotypic changes in SMCs to promote atherosclerosis. We benchmarked the RNA quality of human coronary arteries from autopsies (n = 7) and explanted hearts (n = 7) and performed Visium spatial gene expression on tissue sections with DIT. Although autopsy samples met the RNA quality standard for Visium (DV200 ≥ 30%), only arteries from explanted hearts exhibited reliable sequencing performance. Genes enriched in TGF-β-mediated remodeling of the extracellular matrix were overrepresented in the intima. SMCs enriched in the intima are dedifferentiated, but unlike those in the atherosclerotic lesions, they are not pro-inflammatory. Our findings indicate that autopsy samples are not ideal to distinguish subtle differences among cell phenotypes. SMCs in thickened intima may lead to lipid retention but not necessarily the onset of atherosclerosis.

Diffuse intimal thickening (DIT) is a pre-clinical stage of atherosclerosis characterized by thickened intima. The molecular basis of its susceptibility to atherogenesis is unknown, and mechanistic investigations cannot be performed in commonly used mouse models, in which DIT does not exist. Vascular smooth muscle cells (SMCs) are the predominant cell type that occupies the intima and media of DIT. The molecular differences between these two layers may reveal the earliest phenotypic changes in SMCs to promote atherosclerosis. We benchmarked the RNA quality of human coronary arteries from autopsies (n=7) and freshly explanted hearts (n=7) and performed Visium spatial gene expression on tissue sections with DIT. Although autopsy samples met the RNA quality standard for Visium (DV200 ≥ 30%), only arteries from freshly explanted hearts exhibited reliable sequencing performance. Genes enriched in TGF-β-mediated remodeling of the extracellular matrix were overrepresented in the intima. SMCs enriched in the intima are dedifferentiated, but unlike those in the atherosclerotic lesions, they are not proinflammatory. Our findings indicate that autopsy samples are not ideal to distinguish subtle differences among cell phenotypes. SMCs in thickened intima may lead to lipid retention but not necessarily the onset of atherosclerosis.