Ocular barriers and innovative therapies for eye diseases and cancer

Main achievements

1. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates retinal endothelial cell dysfunction triggered by inflammation.

2. Sitagliptin improves oxidative stress and ameliorates glomerular lesions in animal model of type 1 diabetes.

3. Novel porphyrin- and phthalocyanine-based photosensitizers show remarkable photodynamic therapy (PDT) efficiency in an in vitro model of bladder cancer.

4. Caveolin-1 modulation increases efficacy of a galacto-conjugated phthalocyanine in bladder cancer cells resistant to PDT.

5. Patients with diabetic retinopathy show changes in tear fluid proteins profile.

Publications

P.M.R. Pereira, W. Rizvi, N.V.S.D.K. Bhupathiraju, N. Berisha, R. Fernandes, J.P.C. Tomé, C.M. Drain. Carbon-1 versus Carbon-3 Linkage of d-Galactose to Porphyrins: Synthesis, Uptake, and Photodynamic Efficiency. Bioconjug. Chem. 2018, 29: 306-315. doi: 10.1021/acs.bioconjchem.7b00636. PMID: 29313666.

A. Gonçalves, L. Almeida, A.P. Silva, C.F. Ribeiro, A.F. Ambrósio, A. Cristóvão, R. Fernandes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates retinal endothelial cell dysfunction triggered by inflammation. Biomed. Pharmacother. 2018; 102:833-838. doi: 10.1016/j.biopha.2018.03.144. PMID: 29605771.

J.T. Ferreira,J. Pina, C.A.F. Ribeiro, R. Fernandes*, J.P.C. Tomé*, M.S. Rodríguez-Morgade*, T. Torres*. Synthesis, characterization and in vitro evaluation of Carbohydrate-containing Ruthenium Phthalocyanines as third generation photosensitizers for Photodynamic Therapy. ChemPhotoChem. 2018; 2: 640-654. doi: 10.1002/cptc.201800065.

A.R. Santiago, R. Boia, I.D. Aires, A.F. Ambrósio, R. Fernandes. Sweet stress: coping with vascular dysfunction in diabetic retinopathy”. Front. in Physiol. “Special issue on the “Oxidative stress revisited – Major role in vascular diseases”. 2018; 9: 820. doi: 10.3389/fphys.2018.00820. PMID: 30057551.

M. Bispo, P.M.R. Pereira, F. Setaro, M.S. Rodríguez-Morgade*, R. Fernandes*, T. Torres*, J.P.C. Tomé*. A Galactose Dendritic Silicon (IV) Phthalocyanine as a Photosensitizing Agent in Cancer Photodynamic Therapy. ChemPlusChem. 2018; 83, 855-860. doi: 10.1002/cplu.201800370. PMID: 31950688.

R. Fernandes, S.D. Viana, S. Nunes, F. Reis. Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy. Biochim. Biophys. Acta Mol. Basis Dis. 2019; 1865: 1876. doi: 10.1016/j.bbadis.2018.09.032. PMID: 30287404.

S.R.G. Fernandes, R. Fernandes, B. Sarmento, P.M.R. Pereira, J.P.C. Tomé. Photoimmunoconjugates: novel synthetic strategies to target and treat cancer by photodynamic therapy. Org. Biomol. Chem. (From the themed collection: Organic & Biomolecular Chemistry HOT article collection) 2019; 17, 2579-2593. doi: 10.1039/c8ob02902d. PMID: 30648722.

C.I.V. Ramos, S.P. Almeida, L.M.O. Lourenço, P.M. Ribeiro, R. Fernandes, M.A.F. Faustino, J.P.C. Tomé, J. Carvalho, C. Cruz, M.G.P.M.S. Neves. Multicharged phthalocyanines as selective ligands for G-Quadruplex DNA structures. Molecules 2019; 24(4): 733. doi: 10.3390/molecules24040733. PMID: 30781675.

A. Cruz, R. Queirós, C. Abreu, C. Barata, R. Fernandes, R. Silva, A.F. Ambrósio, R. Soares-dos-Reis, J. Guimarães, M.J. Sá, J.B. Relvas, P.P. Freitas, I.M. Pinto.Electrochemical immunosensor for TNFα-mediated inflammatory disease screening. ACS Chem. Neurosci. 2019; 10 (6): 2676-2682. doi: 10.1021/acschemneuro.9b00036. PMID: 30985099.

C. Marques, A. Gonçalves, P.M.R. Pereira, D. Almeida, B. Martins, C. Fontes-Ribeiro, F. Reis, R. Fernandes. The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes. Life Sci. 2019; 234: 116738. doi.org/10.1016/j.lfs.2019.116738. PMID: 31398418.

J.T. Ferreira, J. Pina, C.A.F. Ribeiro, R. Fernandes*, J.P.C. Tomé*, M. Salomé Rodríguez-Morgade*, T. Torres*. Highly Efficient Singlet Oxygen Generators Based on Ruthenium Phthalocyanines: Synthesis, Characterization and in vitro Evaluation for Photodynamic Therapy. Chemistry – A European Journal. 2020; 26: 1789-1799. doi: 10.1002/chem.201903546. PMID: 31922634.

I. Preguiça, A. Alves, S. Nunes, P. Gomes, R. Fernandes, S. D. Viana, F. Reis. Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy. Nutrients. 2020; 12:250. doi.org/10.3390/nu12010250. PMID: 31963709.

A.T.P.C. Gomes*, R. Fernandes*, C.F. Ribeiro, J.P. Tomé, M.G.M.S. Neves, F.C. Silva, V. Ferreira, J.A.S. Cavaleiro*. Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives. Molecules. 2020; 25: 1607. doi:10.3390/molecules25071607. PMID: 32244514.

P. M.R. Pereira, B. Parada, T. M. Ribeiro-Rodrigues, C.A. Fontes-Ribeiro, H. Girão, J.P.C. Tomé e R. Fernandes. Caveolin-1 modulation increases efficacy of a galacto-conjugated phthalocyanine in bladder cancer cells resistant to photodynamic therapy. Mol. Pharm. 2020; 17: 2145. doi.org/10.1021/acs.molpharmaceut.0c00298. PMID: 32339462.

C.H. Alves, R. Fernandes, A.R. Santiago, A.F. Ambrósio. Microglia contribution to the regulation of the retinal and choroidal vasculature in age-related macular degeneration. Cells. 2020; 9: 1217. doi: 10.3390/cells9051217. PMID: 32423062.

I. Preguiça, A. Alves, S. Nunes, R. Fernandes, P. Gomes, S. D. Viana, F. Reis. Diet-induced rodent models of obesity-related metabolic disorders – a guide to a translational perspective. Obes. Rev. 2020; 21: e13081. doi/10.1111/obr.13081. PMID: 32691524.

B. Martins, M. Amorim, F. Reis, A.F. Ambrósio, R. Fernandes. Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy. Antioxidants. 2020; 9 (8), 705. doi: 10.3390/antiox9080705. PMID: 32759750.

S. Nunes, S.D. Viana, I. Preguiça, A. Alves, R. Fernandes, J.S. Teodoro, A. Figueirinha, L. Salgueiro, S. Silva, I. Jarak, R.A. Carvalho, C. Cavadas, A.P. Rolo, C.M. Palmeira, M.M. Pintado, F. Reis. Blueberry consumption challenges hepatic mitochondrial bioenergetics and elicits transcriptomics reprogramming in healthy Wistar rats. Pharmaceutics, 2020; 12:1094. doi:10.3390/pharmaceutics12111094. PMID: 33202669.

W. Borzęcka, P.M.R. Pereira, R. Fernandes*, T. Trindade*, T. Torres*, J.P.C. Tomé*. Encapsulation of glycosylated porphyrins in silica nanoparticles to enhance the efficacy of cancer photodynamic therapy. Materials Advances. 2021, 2, 1613-1620. doi: 10.1039/d0ma00830c.

A.T.P.C. Gomes, M.G.P.M.S. Neves, R. Fernandes, C.F. Ribeiro, J.A.S. Cavaleiro, N.M.M. Moura. Unraveling the photodynamic activity of cationic benzoporphyrin-based photosensitizers against bladder cancer cells. Molecules. 2021, 26: 5312. doi: 10.3390/molecules26175312. PMID: 34500746.

J.T. Ferreira, J. Pina, C.A.F. Ribeiro, R. Fernandes, J.P.C. Tomé, T. Torres, M.S. Rodríguez-Morgade. A Ruthenium phthalocyanine functionalized with a folic acid unit as a photosensitizer for photodynamic therapy: Synthesis, characterization and in vitro evaluation. J. Porphyr. Phthalocyanines. 2021, 25(10n12): 1193-1202. doi:10.1142/S1088424621501224.

S. Nunes, S.D. Viana, I. Preguiça, A. Alves, R. Fernandes, J.S. Teodoro, P. Matos, A. Figueirinha, L. Salgueiro, A. André, S. Silva, I. Jarak, R.A. Carvalho, C. Cavadas, A.P. Rolo, C.M. Palmeira, M.M. Pintado, Flávio Reis. Blueberry counteracts prediabetes in a hypercaloric diet-induced rat model and rescues hepatic mitochondrial bioenergetics. Nutrients. 2021, 13: 4192. doi.org/10.3390/nu13124192. PMID: 34959746.

W. Borzęcka, P.M.R. Pereira, R. Fernandes*, T. Trindade*, T. Torres*, J.P.C. Tomé*. Spherical and rod silica nanoparticle to transport and deliver photosensitizers into tumor tissues during in vitro photodynamic therapy. J. Mater. Chem. B. 2022, 10: 3248-3259. doi: 10.1039/d1tb02299g. PMID: 35084012.

M. Vieira, R. Fernandes, A.F. Ambrósio, V, Cardoso, M. Carvalho, P.W. Kung, M. Neves e I.M. Pinto. Lab-on-a-chip technologies for minimally invasive molecular sensing of diabetic retinopathy. Lab Chip. 2022; 22: 1876-1889. doi: 10.1039/D1LC01138C. PMID: 35485913.

M. Amorim, B. Martins, F. Caramelo, C. Gonçalves, G. Trindade, J. Simão, P. Barreto, I. Marques, E. Leal, E. Carvalho, F. Reis, T. Ribeiro-Rodrigues, H. Girão, P. Rodrigues-Santos, C. Farinha, A. F. Ambrósio, R. Silva, R. Fernandes. Putative biomarkers in tears for diabetic retinopathy diagnosis. Front. Med. 2022; 9: 873483. doi: 10.3389/fmed.2022.873483. PMID: 35692536.

S. Oliveira, T. Monteiro-Alfredo, R. Henriques, C. Fontes-Ribeiro, R. Seiça, T. Cruz, C. Cabral, R. Fernandes, F. Piedade, M.P. Robalo, P. Matafome, S. Silva. Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes. Int. J. Mol. Sci. 2022; 23: 5652. doi.org/10.3390/ijms23105652. PMID: 35628465.

J.C. Pereira, P.M.R. Pereira, S. Beirão, H. Girão, J.P.C. Tomé*, R. Fernandes*. Photodynamic effect of a galactodendritic porphyrin on cytoskeletal network of human bladder cancer cells. J. Porphyr. Phthalocyanines. 2023; 27: A-H. doi: 10.1142/S1088424623500165.

I.R. Rego, D. Silvério, M.I. Eufrásio, S.S. Pinhanços, B.L. da Costa, J. Teixeira, H. Fernandes, Y. Kong, Y. Li, S.H. Tsang, P.J. Oliveira, R. Fernandes, P.M.J. Quinn, P.F. Santos, A.F. Ambrósio, C.H. Alves. TRAP1 is expressed in human retinal pigment epitelial cells and is required to maintain their energetic status. Antioxidants. 2023; 12: 381. doi.org/10.3390/antiox12020381.

S.N. Pedro, A.T.P.C. Gomes, C. Vilela, C. Vitorino, R. Fernandes, A. Almeida, M.H. Amaral, M.G. Freire, A.J.D. Silvestre, C.S.R. Freire. Thermo-responsive microemulsions containing deep eutectic-based antibiotic formulations for improved treatment of resistant bacterial ocular infections. Advanced Therapeutics. (aceite para publicação)

B. Martins and R. Fernandes. Retinal Degenerative Diseases. Adances in Experimental Medicine and Biology. Vol. 1415, Chapter 4: Disturbed matrix metalloproteinases activity in age-related macular degeneration. Ed. John Ash, 2023. (in press)

Scientific interests and ongoing research projects

Rosa Fernandes’ research interests are mainly focused on the study of blood-retinal barrier impairment in retinal degenerative diseases, namely diabetic retinopathy and age-related macular degeneration (AMD). In particular, she has been interested in investigating the contribution of small extracellular vesicles to the dysfunction of the retinal pigment epithelial cells (disruption of the outer blood-retinal barrier, epithelial-mesenchymal transition, metabolic reprogramming) and neovascularization in AMD.

Other scientific interests:

- Identification of biomarkers in tear fluid that could aid early diagnosis and monitor therapeutic interventions in diabetic retinopathy and AMD.

- Evaluation of the efficacy of novel photosensitizers for photodynamic therapy (PDT) in AMD and bladder cancer.

Team

Group Leader

RF

Rosa Fernandes

PhD Members

RF

Rosa Fernandes

PhD Students

BM

Beatriz Martins

SB

Sandra Beirão

Other members

MP

Maria Pires

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