Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs), with intraocular pressure (IOP) being its primary risk factor. Despite controlling IOP, the neurodegenerative process often continues. Therefore, substances with neuroprotective, antioxidant, and anti-inflammatory properties could protect against RGC death. This study investigated the neuroprotective effects on RGCs and visual pathway neurons of a compound consisting of citicoline and coenzyme Q10 (CoQ10) in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Four groups of mice were used: vehicle group (n = 6), citicoline + CoQ10 group (n = 6), laser–vehicle group (n = 6), and laser–citicoline + CoQ10 group (n = 6). The citicoline + CoQ10 was administered orally once a day starting 15 days before laser treatment, continuing until sacrifice (7 days post-laser). Retinas, the dorsolateral geniculate nucleus (dLGN), the superior colliculus (SC), and the visual cortex (V1) were analyzed. The citicoline + CoQ10 compound used in the laser–citicoline + CoQ10 group demonstrated (1) an ocular hypotensive effect only at 24 h post-laser; (2) prevention of Brn3a+ RGC death in OHT eyes; and (3) no changes in NeuN+ neurons in the dLGN. This study demonstrates that the oral administration of the citicoline + CoQ10 combination may exert a neuroprotective effect against RGC death in an established rodent model of OHT.

Background/Objectives: The loss of retinal ganglion cells (RGCs) is a hallmark of glaucoma, a major cause of blindness. Glial cell activation due to increased intraocular pressure (IOP) significantly contributes to RGC death. Therefore, substances with anti-inflammatory properties could help prevent that process. This study investigated whether combining Citicoline and Coenzyme Q10 (CoQ10) can reduce glial activation in the retina and the rest of the visual pathway, potentially preventing neurodegeneration in a mouse model of unilateral laser-induced ocular hypertension (OHT). Methods: Four groups of mice were used: vehicle (n = 12), CitiQ10 (n = 12), OHT–vehicle (n = 18), and OHT–CitiQ10 (n = 18). The administration of Citicoline and CoQ10 was performed orally once a day, initiated 15 days prior to the laser treatment and maintained post-treatment until sacrifice (3 days for retina or 7 days for the rest of the visual pathway). The retina, dorsolateral geniculate nucleus, superior colliculus, and visual cortex (V1) were immunohistochemically stained and analyzed. Results: In the laser–CitiQ10 group, the Citicoline + CoQ10 compound revealed (1) an IOP decrease at 24 h and 3 days post-laser; and (2) reduced signs of macroglial (decreased GFAP area) and microglial (soma size, arbor area, microglia number, P2RY12 expression) activation in the retina and in the rest of the visual pathway (reduced activated microglial phenotypes and lower GFAP expression). Conclusions: This study shows that oral administration of Citicoline and CoQ10 can reduce glial activation caused by increased IOP in retina and visual pathway in a mouse model of OHT, potentially protecting RGCs from OHT-induced inflammation.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

This study evaluated the early structural and functional effects of combined citicoline and coenzyme Q10 (CoQ10) (CitiQ10) treatment in a laser-induced ocular hypertension (OHT) model in Swiss albino mice, focusing on retinal inflammation and neuroprotection. Sixty male CD-1 mice were assigned to four groups: vehicle, CitiQ10, OHT, and OHT + CitiQ10. OHT was induced by laser photocoagulation of limbal and episcleral veins, and CitiQ10 was administered orally starting 15 days before induction. Intraocular pressure (IOP) was measured by rebound tonometry, retinal structure was assessed by spectral domain optical coherence tomography (SD-OCT), and function was evaluated using full-field electroretinography (ffERG). At 3 days post-induction, OHT eyes exhibited significant retinal nerve fiber layer (RNFL) thickening, increased vitreous particles, and early functional impairment, particularly reduced scotopic b-wave and oscillatory potentials. CitiQ10 treatment mitigated these changes, reducing vitreous particles, moderating RNFL alterations, and not exhibiting significant changes in ERG amplitudes. At 7 days post-induction, structural and functional deficits persisted but were less pronounced in treated eyes. These findings suggest that CitiQ10 treatment may attenuate early retinal damage in glaucoma, with OCT and ffERG serving as reliable monitoring tools, supporting the therapeutic potential of this approach in early stage disease.