Differences in the expression of tau isoforms in dry age-related macular degeneration
Shermin Lak1 , Zahra-Soheila Soheili1 , Mozhgan Rezaei Kanavi2 , Hamid Ahmadieh2 , Fatemeh Suri2 *
- National Institute of Genetic Engineering and Biotechnology,Tehran,Iran.
- Ophthalmic Research Center,Shahid Beheshti University of Medical Sciences,Tehran.Iran.
Abstract: AMD (age-related macular degeneration), the leading cause of central visual loss in developed countries, is a late-onset neurodegenerative retinal disease with pathological similarities with Alzheimer's disease (AD). The molecular mechanisms underlying the disease are not fully known. AMD includes two types, dry and wet, with no effective treatment for the dry type. Tauopathy plays an important role in many neurodegenerative diseases, such as AD. Tau is encoded by the microtubule-associated protein tau (MAPT) with six splice variants. Tau isoforms are classified based on the inclusion of exon 10, which encodes for the second microtubule-binding repeat, into two groups, including three-repeat tau (3R tau) and four-repeat tau (4R tau). The change in the expression of tau and the ratio of 4R/3R tau has been reported for several neurodegenerative diseases. But so far, there has been no report about tau mRNA expression in AMD. In this study, we investigated the expression of tau transcript variants in dry AMD patients for the first time.
Methods: Human donor eye globes were provided by the Iran Eye Bank and classified into three groups, including dry AMD diagnosed individuals (mean age of 72, n = 10), elderly healthy donors (≥50 years, n = 10) as the age-matched controls, and young healthy donors (≤30 years, n = 10) for assessment of the age-associated changes. Total RNA was extracted from the retina of the globes, and real-time PCR was used to assess the expression of total tau isoforms, 3R, and 4R transcript variants by specific primers.
Results: Dry AMD samples contained mixed 3R/4R tau isoforms without any significant difference in total tau transcript variants in comparison with old and young controls. In contrast, there was a significant change in the ratio of 4R/3R tau between dry AMD donors compared to the young controls, while this change was not significant in the elderly controls compared to the young controls.
Conclusion: This report shows that changes in the ratio of 4R/3R tau may be important in the development of dry AMD and may set off specific signaling pathways that help the disease start and get worse. These findings can be studied further in different stages of the disease.
