# Ceruloplasmin and Ferritin Changes in Ocular Fluids from Patients with Vitreoretinal Diseases: Relation with Neuroinflammation and Drusen Formation

**Authors:** Graziana Esposito, Pamela Cosimi, Bijorn Omar Balzamino, Marisa Bruno, Rosanna Squitti, Lucia Dinice, Fabio Scarinci, Mauro Ciro Antonio Rongioletti, Andrea Cacciamani, Alessandra Micera

PMC · DOI: 10.3390/ijms26136307 · International Journal of Molecular Sciences · 2025-06-30

## TL;DR

This study investigates how ceruloplasmin and ferritin levels in eye fluids may indicate early signs of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

## Contribution

The study introduces ocular fluid CP/FT ratios as potential biomarkers for early neurodegeneration and drusen formation.

## Key findings

- CP and FT levels in ocular fluids varied with vitreoretinal conditions and neuroinflammatory markers.
- A higher CP/FT ratio was linked to increased risk of neurodegenerative diseases.
- CP/FT profiles correlated with markers like VEGF, IL-6, NGF, and BDNF.

## Abstract

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer’s, Parkinson’s, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60–85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer’s disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio’s association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history.

## Linked entities

- **Proteins:** ferritin (soma ferritin-like), IL6 (interleukin 6), IL4 (interleukin 4)
- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, CP (ceruloplasmin) [NCBI Gene 1356] {aka AB073614, CP-2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}
- **Diseases:** Alzheimer's, Parkinson's, (MESH:D010300), MH (MESH:D012167), AD (MESH:D000544), VR disorders (MESH:D058499), Vitreoretinal Diseases (MESH:D012164), Drusen (MESH:D015593), neurodegenerative conditions (MESH:D019636), dementias (MESH:D003704), Neuroinflammation (MESH:D000090862), ERMs (MESH:D019773)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12250406/full.md

## References

74 references — full list in the complete paper: https://tomesphere.com/paper/PMC12250406/full.md

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Source: https://tomesphere.com/paper/PMC12250406