Literature Update: Fucoxanthin Protects Retinal Ganglion Cells in an Experimental Glaucoma Model via Regulation of Parkin-Mediated Mitophagy.
Release time:
2025-09-25
In studies of experimental glaucoma models, the Icare TonoLab rodent tonometer has been proven to be an efficient and reliable tool for monitoring intraocular pressure (IOP) in rats.
Objective
Glaucoma is a common neurodegenerative disease resulting in irreversible blindness. This study investigates whether fucoxanthin can safeguard retinal ganglion cells (RGCs) by modulating Parkin-mediated mitophagy in experimental glaucoma.
Methods
An experimental glaucomatous model was induced in Sprague-Dawley rats via translimbal laser photocoagulation. Intraocular pressure (IOP) was monitored using a Tonolab tonometer. RGC survival was evaluated through FluoroGold labelling. Retinal and optic nerve samples were analysed at 3 days and 2 weeks post-IOP elevation for mitochondrial morphology and gene/protein expression using immunohistochemistry and molecular assays.
Results
Results demonstrated that mitophagy was acutely overactivated in the short term and impaired over the long term in ocular hypertensive rats. Fucoxanthin intravitreal administration enhanced RGC survival and Bcl-2 expression while reducing Bax and glial fibrillar acidic protein levels. During acute IOP elevation, fucoxanthin curtailed Parkin expression and mitophagosome formation, mitigating excessive mitophagy. Under prolonged IOP elevation, it elevated mitophagy-related proteins and restored mitophagy function, contributing to damaged mitochondrial clearance.
Figure 1. Effect of fucoxanthin on RGC survival in ocular hypertensive rat retinas. The retinal flat mounts of blank control rats (A, D and G), vehicle-treated ocular hypertensive rats (B, E and H) and fucoxanthin-treated ocular hypertensive rats (C, F and I). Quantitative analysis of RGC survival (J) (n=6; data are expressed as mean±SD; **p<0.01; scale bar=100 µm (A–I)). (K) Proposed mechanism by which fucoxanthin mitigates RGC loss in glaucomatous rats by modulating Parkin-mediated mitophagy (created by biorender.com). LAMP1, lysosomal-associated membrane protein 1; LC3, microtubule-associated protein 1A/1B-light chain 3; NC, normal control; OHT, ocular hypertension; OHT+FX, fucoxanthin-treated ocular hypertension; RGC, retinal ganglion cell.
Figure 2. Impact of fucoxanthin on apoptotic protein expression and Müller glial activation in glaucomatous rats. In untreated ocular hypertensive retinas, GFAP (B) and Bax (D) protein levels were elevated, while Bcl-2 (F) levels were reduced at both 3 days and 2 weeks post-IOP elevation. Fucoxanthin treatment resulted in a decrease in GFAP levels at both time points compared with vehicle-treated groups (B). Bax levels initially increased at 3 days but decreased at 2 weeks following fucoxanthin treatment (D), whereas Bcl-2 expression showed an increase at 14 days (F). At the mRNA level, ocular hypertensive retinas exhibited increased GFAP (C) and Bax (E) mRNA levels, with GFAP elevated at both 3 days and 2 weeks, and Bax increased at 2 weeks. Conversely, Bcl-2 (G) mRNA was decreased at both time points. Fucoxanthin treatment led to a reduction in GFAP mRNA at 3 days and 2 weeks, a decrease in Bax mRNA at 2 weeks and an increase in Bcl-2 mRNA at both 3 days and 2 weeks compared with the vehicle-treated group (n=3; data are expressed as mean±SD; *p<0.05; **p<0.01). BAX, Bcl-2 associated X protein; Bcl-2, B-cell lymphoma-2; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFAP, glial fibrillar acidic protein;mRNA, messenger RNA; NC, normal control; OHT, ocular hypertension; OHT+FX, fucoxanthin-treated ocular hypertension.
Figure 3. Effect of fucoxanthin on mitophagy marker expression in glaucomatous rats. In untreated ocular hypertensive retinas, mRNA levels of Parkin (A), optineurin (B) and LAMP1 (D) increased at 3 days but decreased at 2 weeks, while LC3 (C) mRNA levels increased at both 3 days and 2 weeks. Following fucoxanthin treatment, mRNA levels of Parkin (A), optineurin (B), LC3 (C) and LAMP1 (D) decreased at 3 days but increased at 2 weeks compared with the vehicle-treated group (n=3; data are expressed as mean±SD; *p<0.05; **p<0.01). (E) Immunofluorescence analysis of Parkin and GFAP expression in vehicle-treated and fucoxanthin-treated ocular hypertensive retinas. Compared with vehicle-treated ocular hypertensive retinas (a–d), GFAP immunoreactivity decreased, whereas Parkin immunoreactivity increased, particularly in the retinal nerve fibre layer of fucoxanthin-treated ocular hypertensive retinas (e–h). Scale bar=50 µm. GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GCL, ganglion cell layer; GFAP, glial fibrillar acidic protein; INL, inner nuclear layer; IPL, inner plexiform layer; LAMP1, lysosomal-associated membrane protein 1; LC3, microtubule-associated protein 1A/1B-light chain 3; mRNA, messenger RNA; NC, normal control; OHT, ocular hypertension; OHT+FX, fucoxanthin-treated ocular hypertension; ONL, outer nuclear layer; OPL, outer plexiform layer.
Figure 4. Effects of fucoxanthin on mitochondrial morphology and mitophagy. (A) Mitochondrial health was assessed using a scoring system based on the appearance of cristae in ultrastructural analyses. (B) NC group, where green arrows indicate healthy mitochondria. (C) OHT group, characterised by yellow arrows pointing to unhealthy mitochondria. (D) OHT+FX group, with red arrows indicating mitophagosomes. Relative to the control group (B), ocular hypertensive optic nerves (C) demonstrated a significant increase in the number of mitochondria (F), autophagosomes (G) and mitophagosomes (H) at both 3 days and 2 weeks post-treatment. Treatment with fucoxanthin resulted in a higher mitochondrial health score (E) and a greater number of mitochondria (F) at 3 days and 2 weeks compared with the vehicle-treated group. Notably, the number of autophagosomes (G) was reduced at 3 days but increased at 2 weeks in the fucoxanthin-treated group (n=3; data are expressed as mean±SD; *p<0.05; **p<0.01). Scale bar=500 nm (B–D). IOP, intraocular pressure; NC, normal control; OHT, ocular hypertension; OHT+FX, fucoxanthin-treated ocular hypertension.
Figure 5. Impact of fucoxanthin on mitophagy-related proteins in glaucomatous rats. Compared with the control group, the protein levels of Parkin (B) and LAMP1 (E) were significantly elevated at 3 days but decreased at 2 weeks. The protein levels of optineurin (C) and the ratio of LC3-II/LC3-I (D) were increased at both 3 days and 2 weeks in the ocular hypertensive optic nerves. In the fucoxanthin-treated group, the protein expression of Parkin (B), optineurin (C), LAMP1 (E) and the ratio of LC3-II/LC3-I (D) was notably reduced at 3 days and increased at 2 weeks compared with the vehicle-treated group (n=3; data are expressed as mean±SD; *p<0.05; **p<0.01). GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LC3, microtubule-associated protein 1A/1B-light chain 3; LAMP1, lysosomal-associated membrane protein 1; NC, normal control; OHT, ocular hypertension; OHT+FX, fucoxanthin-treated ocular hypertension.
Conclusion
Fucoxanthin exerts neuroprotective effects in experimental glaucoma by modulating Parkin-mediated mitophagy. This highlights the therapeutic potential of maintaining mitophagy homeostasis for glaucoma treatment.
References： https://pubmed.ncbi.nlm.nih.gov/40841125
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