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Retinal Degeneration in MPS-IIIA Mouse Model
Daniela Intartaglia1, Giuliana Giamundo1, Elena Marrocco1
1Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
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.
Insights
Mucopolysaccharidosis type IIIA (MPS-IIIA) causes progressive retinal dystrophy due to heparan sulfate accumulation and impaired autophagy. This study details the retinal pathology in MPS-IIIA mice, aiding diagnosis and therapy development.
Area of Science:
- Lysosomal storage disorders
- Neurodegenerative diseases
- Ophthalmology
Background:
- Mucopolysaccharidosis type IIIA (MPS-IIIA) is a severe lysosomal storage disorder (LSD) resulting from sulfamidase deficiency.
- It leads to heparan sulfate accumulation, causing multisystemic issues, notably severe central nervous system (CNS) impairment and visual deficits.
Purpose of the Study:
- To characterize retinal morphology and function in an MPS-IIIA mouse model.
- To investigate the impact of SGSH deficiency on autophagic flux in the retina.
Main Methods:
- Phenotypic analysis of retinal morphology and function in MPS-IIIA mice.
- Assessment of heparan sulfate (HS) accumulation.
- Evaluation of autophagic flux and apoptotic processes.
- Analysis of microgliosis in the retina.
Main Results:
- MPS-IIIA mice displayed progressive retinal dystrophy with significant visual function decline.
- Photoreceptor degeneration correlated with HS accumulation and blocked autophagy.
- Reactive microgliosis and apoptosis were observed in the retinas of MPS-IIIA mice.
Conclusions:
- This study presents the first comprehensive retinal disorder spectrum in MPS-IIIA.
- Findings contribute to understanding visual impairment in MPS-IIIA and support diagnosis, counseling, and therapeutic strategies.
