/ Research Lines

Ocular barriers and innovative therapies for eye diseases and cancer

About


We aim to understand and develop innovative solutions for chronic diseases that predominantly affect the elderly. Our research focuses on two key areas: degenerative retinal diseases and bladder cancer. By addressing the complex mechanisms underlying these conditions, we aim to contribute to better diagnostics, treatments, and quality of life for patients.

Research Focus

Degenerative Retinal Diseases

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of blindness in adults, both linked to the disruption in the blood-retinal barrier (BRB).

  • Diabetic retinopathy (DR): We investigate how inner BRB permeability increases during early DR stages and explore abnormal blood vessel growth in advanced stages. Our goal is to identify early interventions and reduce reliance on invasive treatments.
  • Age-related macular degeneration (AMD): We study the transition from dry to neovascular AMD, which causes irreversible vision loss, focusing on retinal pigment epithelial (RPE) cells dysfunction and outer BRB alterations.

We also explore tear fluid biomarkers as a non-invasive diagnostic tool for retinal diseases.

Bladder Cancer Research

Bladder cancer is a prevalent cancer with high recurrence rates and significant treatment challenges. We are evaluating new photosensitizing agents for theranostics, combining diagnostic imaging with photodynamic therapy to target tumors more effectively and reduce side effects.

Scientific Goals

i) Unravel the molecular and cellular mechanisms driving AMD and DR progression to develop novel therapeutic strategies.

ii) Identify tear fluid biomarkers for early diagnosis and stratification of retinal diseases.

iii) Innovate photodynamic therapy approaches for bladder cancer.

Using preclinical models and human biological samples, our multidisciplinary approach bridges fundamental research with clinical applications, striving to advance healthcare for these debilitating

Main achievements


  • In a cross-sectional, non-interventional study, we showed altered tear fluid protein profiles in diabetic patients with retinopathy (non proliferative diabetic retinopathy and proliferative diabetic retinopathy) compared to healthy controls, and identified tear fluid as a rich source of small extracellular vesicles.

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

  • We demonstrated that caveolin-1 modulation significantly enhances the therapeutic efficacy of a galacto-conjugated phthalocyanine in bladder cancer cells resistant to PDT.

  • We identified cytoskeletal rearrangements mediated by galectin-1 and RhoA as key factors underlying resistance to the PDT effect of a porphyrin conjugated with dendritic galactose units.

Team

PhD Students

Beatriz Martins

PhD Student in Health Sciences, FMUC

Sandra Beirão

PhD Student in Chemistry, IST

MSc Students

CB
Cátia Silva, BSc

MSc Student, MIB, FMUC

Marta Santos, BSc

MSc Student, Master in Pharmacy, ESTES

Publications

Scientific interests and ongoing research projects


1. Extracellular vesicles and age-related macular degeneration (AMD)
We are uncovering the role of extracellular vesicles (EVs) in driving dysfunction of the retinal pigment epithelial (RPE) cells (outer blood retinal barrier breakdown, epithelial-mesenchymal transition, metabolic reprogramming) and choroidal neovascularization in AMD.

We are currently investigating how EVs secreted by senescent RPE regulate the local senescent microenvironment and facilitate intercellular communication, contributing to AMD progression.

2. Molecular biomarkers in tear fluid for retinal degenerative diseases
We showed that tear fluid is a valuable source of biomarkers for the diagnosis and stratification of retinal diseases like diabetic retinopathy (DR); we also showed changes in the protein profile of the tears of diabetic patients with retinopathy.

Currently, we are interested in using multi-omics approaches, including metabolomics and transcriptomics, to identify biomarkers in tear fluid. This work aims to aid the diagnosis, patient stratification, and monitoring of treatment responses in retinal degenerative diseases linked to blood retinal barrier breakdown.

3. Develop innovative therapeutic strategies for AMD and DR
We are developing advanced drug delivery systems to optimize therapies for AMD and diabetic retinopathy. Our strategies incorporate therapeutic agents with anti-inflammatory, antioxidant, and antiangiogenic properties to improve treatment efficacy.

4. Photodynamic therapy
For AMD, we are currently engineering surface-functionalized exosomes for targeted therapies in AMD. Our focus is on multi-targeting strategies and photodynamic therapy to address subretinal fibrosis.

For bladder cancer, we are investigating novel glyco-conjugated photosensitizers for targeted photodynamic therapy (tPDT). This includes theranostic applications and studies on cellular localization to enhance precision and efficacy.

Funded projects


ExoSwitch – Understanding the switch between dry and wet age-related macular degeneration: role of exosomes

Funding: Global Ophthalmology Awards Program from Bayer | November 2018 - August 2022