Our group studies the molecular mechanisms involved in retinal diseases with the aim of developing new genetic and pharmacological therapeutic strategies. We combine expertise in retinal cell biology, both in normal and pathological conditions.
The Retinal Pigment Epithelium (RPE) is a highly specialized layer of cells, representing a fundamental component of the visual unit. We are interested in understanding the role of RPE lysosomal dysfunction on retinal degeneration. Also, we are exploring a new therapeutic strategy for age-related macular degeneration (AMD).
AMD causes a progressive impairment of the central vision and is the leading cause of irreversible blindness in developed countries and is currently incurable. In a project funded by “La Caixa Foundation” we aim to target NRF2, a major regulator of several cellular processes such as oxidative stress response and autophagy and identify new molecules with pharmacological interest.
We also study Choroideremia, a rare X-linked form of retinal degeneration, and studying how mutations in the leading gene, REP1, impact on RPE lysosomal function, vesicular trafficking and cell death mechanisms.
We also have a project investigating the role of RPE melanin in AMD protection. In close collaboration with ophthalmologists, orthoptists and bioinformatics we are also developing new tools for the identification of imagiologic biomarkers for intermediate AMD and other retinal diseases.
Projects
- 2023.12358.PEX (FCT, Portugal) - Is melanin protective in Age-related macular degeneration? (MelPro-AMD) (50K€).
Evidence suggests that melanin could exert a protective function in the context of AMD and other degenerative diseases of the retina. The goal of this project is to establish whether RPE melanin can contribute to reduce the formation and/or clearance of lipofuscin and the molecular mechanisms that regulate this protective functional.
- 31-05-26- HR22-00569-NRF2 as a novel therapeutic target in early and intermediate age-related macular degeneration- La caixa Foundation (980K€)
Using NRF2 activators as a potential therapeutic approach for Early AMD. We will dissect the molecular mechanisms underlying the prevention and/or clearance of autofluorescent granule load in RPE models by macroautophagy and the anti-oxidative stress response. Lead compounds resulting from the in vitro studies will be validated in mouse models of AMD.
Publications
- Coelho R, Antas P, Fonseca AF, Oliveira D, Carvalho C, Pedro ML, Hall MJ, Falcão AS, Seabra MC, Lopes-da-Silva M. Loss of REP-1 in retinal pigment epithelial cells leads to impaired phagosome processing and altered lysosomal pathway function.. Mol Biol Cell. 2025 Sep 1;36(9):ar116. doi: 10.1091/mbc.E24-11-0497. PMID: 40768322
- Falcão AS, Pedro ML, Tenreiro S, Seabra MC.Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.. Antioxidants (Basel). 2025 May 16;14(5):596. doi: 10.3390/antiox14050596. PMID: 40427478
- Rojo AI, Buttari B, Cadenas S, Carlos AR, Cuadrado A, Falcão AS, López MG, Georgiev MI, Grochot-Przeczek A, Gumeni S, Jimenez-Villegas J, Horbanczuk JO, Konu O, Lastres-Becker I, Levonen AL, Maksimova V, Michaeloudes C, Mihaylova LV, Mickael ME, Milisav I, Miova B, Rada P, Santos M, Seabra MC, Strac DS, Tenreiro S, Trougakos IP, Dinkova-Kostova AT. Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.. Redox Biol. 2025 Feb;79:103464. doi: 10.1016/j.redox.2024.103464. Epub 2024 Dec 16. PMID: 39709790
- Fonseca AF, Coelho R, da-Silva ML, Lemos L, Hall MJ, Oliveira D, Falcão AS, Tenreiro S, Seabra MC, Antas P. Modeling Choroideremia Disease with Isogenic Induced Pluripotent Stem Cells.. Stem Cells Dev. 2024 Oct;33(19-20):528-539. doi: 10.1089/scd.2024.0105. Epub 2024 Aug 16. PMID: 39078329
- Neto MV, De Rossi G, Berkowitz BA, Seabra MC, Luthert PJ, Futter CE, Burgoyne T. Daily Light Onset and Plasma Membrane Tethers Regulate Mitochondria Redistribution within the Retinal Pigment Epithelium. Cells. 2024 Jun 25;13(13):1100. doi: 10.3390/cells13131100. PMID: 38994953
- Carvalho C, Lemos L, Antas P, Seabra MC. Gene therapy for inherited retinal diseases: exploiting new tools in genome editing and nanotechnology.. Front Ophthalmol (Lausanne). 2023 Sep 19;3:1270561. doi: 10.3389/fopht.2023.1270561. eCollection 2023. PMID: 38983081
- Antas P, Carvalho C, Cabral-Teixeira J, de Lemos L, Seabra MC. Toward low-cost gene therapy: mRNA-based therapeutics for treatment of inherited retinal diseases. Trends Mol Med. 2023 Dec 2:S1471-4914(23)00271-X. doi: 10.1016/j.molmed.2023.11.009. Online ahead of print. PMID: 38044158
- Cardoso MH, Hall MJ, Burgoyne T, Fale P, Storm T, Escrevente C, Antas P, Seabra MC, Futter CE. Impaired Lysosome Reformation in Chloroquine-Treated Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 2023 Aug 1;64(11):10. doi: 10.1167/iovs.64.11.10. PMID: 37548963
- Flores R, Fradinho AC, Pereira RS, Mendes JM, Seabra MC, Tenreiro S, Carneiro Â. Identifying Imaging Predictors of Intermediate Age-Related Macular Degeneration Progression.. Transl Vis Sci Technol. 2023 Jul 3;12(7):22. doi: 10.1167/tvst.12.7.22. PMID: 37490304
- Escrevente C, Falcão AS, Hall MJ, Lopes-da-Silva M, Antas P, Mesquita MM, Ferreira IS, Cardoso MH, Oliveira D, Fradinho AC, Ciossek T, Nicklin P, Futter CE, Tenreiro S, Seabra MC. Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction.. Invest Ophthalmol Vis Sci. 2021 Jul 1;62(9):39. doi: 10.1167/iovs.62.9.39. PMID: 34313720
Prizes and Awards
- 2024 NOVA Research Impact Narratives Challenge (To MS)
- 2024 Career Award, Portuguese Biochemical Society (To MS)
- 2024 European Society for Pigment Cell Research Prize (To MS)
- 2024 Bluepharma Innovation Award (To MS)
- 2015 Grande Prémio BIAL de Medicina, Portugal (To MS)
Open Positions
Research Grant (BI), for the conduct of R&D activities by a graduate with a Master degree enrolled in a course non-leading to an academic degree - Ref. ª SAI/2025/07
There is an open call for applications for a Research Grant (BI), for the conduct of R&D activities by a graduate with a Master degree enrolled in a course non-leading to an academic degree, under reference SAI/2025/07 in the scope of PI - IF - 2023.12358.PEX - MelPro-AMD project, at the institution Faculdade de Ciências Médicas|NOVA Medical School (FCM|NMS) from Universidade NOVA de Lisboa (UNL), supported by income from the above mentioned project, financed by the Fundação para a Ciência e a Tecnologia, I.P.).
Field of study: Cellular Biology/Biomedicine
Link for EURAXESS: Notice SAI/2025/07
Colaborations
- Antonio Cuadrado, Universidad Autónoma de Madrid, Spain
- Clare Futter, Institute of Ophthalmology, UCL, London, UK
- Graça Raposo, Institut Curie, Paris, France
- Giovanni Vozzi, Università di Pisa – Centro di Ricerca “E. Piaggio”, Pisa, Italy
- Wojciech Swieszkowski, Warsaw University of Technology, Warsaw, Poland
- Eugene Smit, SNC Fibers, South Africa
- Miguel Veja, Allinky Biopharma, Spain
- David Gamm, Un. Wisconsin, Madison, USA