Abstract
Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo A) is one of the most severe lysosomal storage disorder (LSD) caused by the inherited deficiency of sulfamidase, a lysosomal sulfatase enzyme involved in the stepwise degradation of heparan sulfates (HS). MPS-IIIA patients show multisystemic problems, including a strong impairment of central nervous system (CNS), mild somatic involvement, and ocular manifestations that result in significant visual impairment. Despite the CNS and somatic pathology have been well characterized, studies on visual system and function remain partially explored. Here, we characterized the retina morphology and functionality in MPS-IIIA mouse model and analyzed how the SGSH deficiency affects the autophagic flux. MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function. The photoreceptor degeneration was associated with HS accumulation and a block of autophagy pathway. These events caused a reactive microgliosis, and a development of apoptotic processes in MPS-IIIA mouse retina. Overall, this study provides the first phenotypic spectrum of retinal disorders in MPS-IIIA and significantly contributes for diagnosis, counseling, and potential therapies development.
Highlights
Mucopolysaccharidoses (MPSs) belong to a group of lysosomal storage disorders (LSDs) caused by the deficiency of lysosomal enzymes involved in the catabolism of complex polysaccharides, the glycosaminoglycans (GAGs)
In order to explore the retinal phenotypic alteration in MPS-IIIA disorders, we carried out a detailed functional and morphological analysis of male MPS-IIIA and age-matched wild type (WT) mice at different time points: 3, 6, 9 months of age according to progression of neuropathology
Our results showed a decrease of a-wave amplitude with a relatively preserved b-wave amplitude in MPS-IIIA mice compared to age-matched WT mice (Figures 1A– C)
Summary
Mucopolysaccharidoses (MPSs) belong to a group of lysosomal storage disorders (LSDs) caused by the deficiency of lysosomal enzymes involved in the catabolism of complex polysaccharides, the glycosaminoglycans (GAGs). Ophthalmic problems are very common in MPS patients with variable severity and age of onset They are associated with the accumulation of GAGs and comprise corneal clouding, glaucoma, atrophy of optic nerve, and retinal dysfunction. The main ocular manifestations reported in MPS-IIIA patients are represented by nerve atrophy, corneal changes, glaucoma, and retinopathy caused by the HS deposition (Fenzl et al, 2015; Wilkin et al, 2016). For this reason, an early diagnosis is crucial for a rapid intervention and amelioration of disease outcome. These events cause the apoptosis-mediated cell death and inflammatory processes in the MPS-IIIA retina
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
