Oxidative stress has been documented to be a key factor in the cause and progression of different retinal diseases. Oxidative cellular unbalance triggers a sequence of reactions which prompt cell degeneration and retinal dysfunction, both hallmarks of several retinal pathologies. There is no effective treatment, yet, for many retinal diseases. Antioxidant treatment have been pointed out to be an encouraging palliative treatment; the beneficial effects documented involve slowing the progression of the disease, a reduction of cell degeneration, and improvement of retinal functions. There is a vast information corpus on antioxidant candidates. In this review, we expose three of the main antioxidant treatments, selected for their promising results that has been reported to date. Recently, the sulforaphane, an isothiocyanate molecule, has been unveiled as a neuroprotective candidate, by its antioxidant properties. Progesterone, a neurosteroid has been proposed to be a solid and effective neuroprotective agent. Finally, the lipoic acid, an organosulfur compound, is a well-recognized antioxidant. All of them, have been tested and studied on different retinal disease models. In this review, we summarized the published results of these works, to offer a general view of the current antioxidant treatment advances, including the main effects and mechanisms described.

Gonadal steroid hormones are critical regulatory substances involved in various developmental and physiological processes from fetal development through adulthood. These hormones, derived from cholesterol, are synthesized primarily by the gonads, adrenal cortex, and placenta. The synthesis of these hormones involves a series of enzymatic steps starting in the mitochondria and includes enzymes such as cytochrome P450 and aromatase. Beyond their genomic actions, which involve altering gene transcription over hours, gonadal steroids also exhibit rapid, nongenomic effects through receptors located on the cell membrane. Additionally, recent research has highlighted the role of these hormones in the central nervous system (CNS). However, the interactions between gonadal steroid hormones and the retina have received limited attention, though it has been suggested that they may play a protective role in retinal diseases. This review explores the synthesis of gonadal hormones, their mechanisms of action, and their potential implications in various retinal and optic nerve diseases, such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), or retinitis pigmentosa (RP), discussing both protective and risk factors associated with hormone levels and their therapeutic potential.

(1) Background: Retinitis pigmentosa (RP) is characterized by progressive photoreceptor death. A Prph2Rd2 or an rds mouse is an RP model that closely reflects human RP. The objective of this study was to investigate the relationship of rod and cone death with oxidative stress and inflammation in rds mice. (2) Methods: The retinas of control and rds mice on postnatal days (PN) 11, 17, 21, 28, 35, and 42 were used. Oxidative damage to macromolecules, glutathione (GSH and GSSG), GSH synthesis enzymes, glial fibrillar acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and cluster of differentiation 68 (CD68) was studied. (3) Results: The time sequence of oxidative stress and inflammation changes in rds mice occurs as follows: (i) At PN11, there is a small increase in photoreceptor death and in the microglial cells; (ii) at PN17, damage to the macromolecules is observed; (iii) at PN21, the maximum photoreceptor death rate is detected and there is an increase in GSH-GSSG and GFAP; (iv) at PN21, the microglial cells are activated; and(v) at PN28, there is a decrease in GSH synthesis enzymes. (4) Conclusions: These findings contribute to the understanding of RP physiopathology and help us to understand whether oxidative stress and inflammation are therapeutic targets. These findings contribute to our understanding that, in RP, oxidative stress and inflammation evolution and their relationship are time-dependent. In this sense, it is important to highlight that both processes are potential therapeutic targets in this disease.

(1) Background: the aim of this work was to study microglia and autophagy alterations in a one retinitis pigmentosa (RP) model at different stages of the disease (when rods are dying and later, when there are almost no rods, and cones are the cells that die. (2) Methods: rd1 mice were used and retinas obtained at postnatal days (PN) 11, 17, 28, 35, and 42. Iba1 (ionized calcium-binding adapter molecule 1) was the protein selected to study microglial changes. The macroautophagy markers Beclin-1, Atg5, Atg7, microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (LAMP2) (involved in chaperone-mediated autophagy (CMA)) were determined. (3) Results: the expression of Iba1 was increased in rd1 retinas compared to the control group at PN17 (after the period of maximum rod death), PN28 (at the beginning of the period of cone death), and PN42. The number of activated (ameboid) microglial cells increased in the early ages of the retinal degeneration and the deactivated forms (branched cells) in more advanced ages. The macroautophagy markers Atg5 at PN11, Atg7 and LC3II at PN17, and Atg7 again at PN28 were decreased in rd1 retinas. At PN35 and PN42, the results reveal alterations in LAMP2A, a marker of CMA in the retina of rd1 mice. (4) Conclusions: we can conclude that during the early phases of retinal degeneration in the rd1 mouse, there is an alteration in microglia and a decrease in the macroautophagy cycle. Subsequently, the CMA is decreased and later on appears activated as a compensatory mechanism.

The intake of antioxidants has increased in the last years in order to treat some pathologies associated with oxidative stress such as cancer, diabetes mellitus, atherosclerosis, myocardial infarction, acute pancreatitis, Parkinson's and Alzheimer's disease among others. In colorectal cancer, a widely antineoplastic drug used is the fluorinated uracil molecule 5-Fluorouracile (5-FU). The aim of this study is to assess the antioxidant capacity observed by the inhibition of lipid peroxidation by 5-FU and other fluorinated uracil derivates: 6-[Difluoro(phenyl)methyl]-3-(2,4,6-trifluorophenyl)pyrimidine-2,4(1H,3H)-dione (S-81), 3-[2-Chloroethyl]-6-[difluoro(phenyl)methyl]pyrimidine-2,4(1H,3H)-dione (S-86), 6-[Difluoro(phenyl)methyl]-3-(4-trifluoromethoxyphenyl)pyrimidine-2,4(1H,3H)-dione (S-123). The results showed a significant decrease in MDA production of 58.12% in S-86, 44.61% in S-123, 24.11% in 5-FU and 10.83% in S-81 in the sample with highest concentration (10µM). 5-FU also showed a Total Antioxidant Capacity of 0.68 Trolox Equivalent Antioxidant Capacity.