👤 Markus M Forsberg

Juvenile neuronal ceroid lipofuscinosis (JNCL) is a rare neurodegenerative disorder caused by mutations in the CLN3 gene and characterized by early vision loss and a progressive neurological decline. To characterize the progression of retinal pathology, we conducted a 15-month study using the Cln3Δex7/8 mouse model which carries the most common causative mutation of JNCL. Retinal function was assessed every three months from the age of 3-15 months using electroretinography (ERG), optical coherence tomography (OCT), fundus imaging, and immunohistochemistry. OCT and fundus imaging in the Cln3Δex7/8 mice revealed a progressive thinning of the inner nuclear layer (INL) and an accumulation of subretinal drusenoid deposits. We detected a progressive loss of rod bipolar cells (RBCs) with immunofluorescence staining which was accompanied by ubiquitin-positive punctae, indicative of a potential role of the ubiquitin-proteasome system (UPS) in the selective loss of RBCs and the associated inner retinal dysfunction. Furthermore, late-stage immune cell activity was observed in the subretinal space of the Cln3Δex7/8 mice. ERG measurements confirmed previous findings of a predominant inner retinal dysfunction and revealed also a more pronounced photoreceptor impairment, as well as an earlier onset of retinal dysfunction than previously reported. These findings provide new insights into the pathological features of retinal degeneration in Cln3Δex7/8 mice, including subretinal drusenoid deposits, tubular subretinal fluid, and ubiquitin accumulation as well as a better overview of the rate of the degeneration process, thus expanding our understanding of JNCL pathogenesis. Show less

Chronic hyperglycemia inflicts serious cellular damage by inducing oxidative stress through the excessive production of free radicals. This oxidative milieu may impair the cellular redox capacity and disrupt the insulin-like growth factor (IGF) system, thereby increasing the risk of cardiovascular complications. This study aimed to investigate plasma levels of components of the IGF system and antioxidant biomarkers in young adults with type 1 diabetes mellitus (T1DM) compared to age-matched healthy controls in Brazil. This study included 129 patients with T1DM (76 female, 53 male; mean age 26.97 ± 0.6 years) and 95 healthy controls (61 female, 34 male; mean age 27.35 ± 0.68 years). Young Brazilian adults with T1DM had significantly lower mean IGF-I and higher mean IGFBP-1 levels compared to healthy controls. The T1DM group showed a more atherogenic profile, characterized by a significantly elevated ApoB/ApoA1 ratio and increased oxidized LDL levels. However, a subset of patients with significantly better glycemic control exhibited serum IGF-I and IGFBP-1 levels within the normal range observed in controls, which may indicate the presence of residual functional beta-cell activity or reflect better glycemic control in this subgroup. Antioxidant components and oxidative stress biomarkers were significantly upregulated in the T1DM group compared to the control group, suggesting a compensatory adaptive response. No significant correlation was observed between biomarkers of oxidative stress and the IGF-system. Show less

Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in exostosin-1 or -2 (EXT1 or EXT2). It is characterized by the formation of multiple benign growing osteochondromas (exostoses) that most commonly affect the long bones; however, it may also occur throughout the body. Although many of these lesions are clinically asymptomatic, some can lead to chronic pain and skeletal deformities and interfere with adjacent neurovascular structures. Here, we report two unrelated probands that presented with a clinical and molecular diagnosis of HME with venous malformation, a clinical feature not previously reported in individuals with HME. Show less