Tabriz University of Medical Sciences

Leber congenital amaurosis (LCA) is a severe inherited retinal disorder that appears in early childhood and represents one of the primary causes of pediatric blindness. More than 25 genes, including NMNAT1, have been linked to this condition.

A 5-year-old boy presenting clinical signs of LCA underwent whole-exome sequencing (WES). Comprehensive ophthalmic assessments, including optical coherence tomography (OCT) and electroretinography (ERG), were performed to evaluate retinal structure and function. In silico prediction tools, conservation analysis, molecular docking, and root mean square fluctuation (RMSF) simulations were used to investigate the structural and functional consequences of the detected variants. Segregation analysis was also performed in available family members.

OCT imaging revealed marked atrophy of the outer retinal layers with disruption of photoreceptor and ellipsoid zones. ERG recordings demonstrated severely reduced scotopic and photopic responses, indicating generalized retinal dysfunction. Two novel compound heterozygous variants in NMNAT1 (NM_022787.4): c.731T > A (p.Val244Asp) and NMNAT1 (NM_022787.4): c.28G > T (p.Val10Phe) were identified. Segregation analysis confirmed a trans configuration. Based on combined evidence, both variants were reclassified according to ACMG guidelines. Structural analysis showed significant alterations in the variant proteins and increased overall stability relative to the wild type. Docking studies demonstrated global and local changes.

These findings introduce two novel NMNAT1 variants linked to LCA9 and underscore the importance of combining clinical data, genetic evaluation, and computational analysis when interpreting rare variants. Further laboratory studies are still needed to clarify their pathogenic roles.

Female reproductive disorders are a leading cause of infertility, affecting millions of women worldwide and resulting in significant emotional and social challenges. Despite advances in medical science, current treatment options are often limited in their ability to restore normal reproductive function, particularly in cases involving hormonal imbalances, complex tissue damage, or unexplained infertility. These limitations highlight the urgent need for innovative and more effective treatment strategies to address the underlying causes of female infertility.

Recent advances in regenerative medicine suggest that stem cell-based therapies, particularly those utilizing mesenchymal stem cells, may offer new hope for addressing infertility-related challenges. However, direct cell therapies face significant limitations within the human body. As a result, cell-free approaches, such as the use of secreted factors from mesenchymal stem cells, have gained attention as promising alternatives. The secretome of these stem cells, which includes cytokines, microRNAs, extracellular vesicles, and other bioactive molecules, plays a vital role in regulating key biological processes such as cell growth, migration, and the formation of new blood vessels. These properties are especially relevant for treating conditions like endometriosis and ovarian dysfunction, both of which are closely associated with infertility. This review examines preclinical studies that have evaluated the safety and therapeutic potential of cell-free treatments derived from mesenchymal stem cells for female infertility.

Although preclinical findings are promising, there is currently limited clinical evidence supporting the use of cell-free therapies for human infertility, and this evidence is still emerging. This review emphasizes the therapeutic potential of MSC secretome in treating female infertility and underscores the necessity for further well-designed clinical studies to support its integration into standard clinical practice.