Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Development of a population pharmacokinetic model for the novel long-acting injectable antipsychotic risperidone ISM®.

AIMS: The aims of this study were to develop a population pharmacokinetic (PK) model for risperidone ISM® and to investigate the relationships between active moiety exposure, as described by apparent clearance (CL40), and several covariates using all data from five clinical studies. METHODS: A population PK model was developed using active moiety concentrations from a study in healthy volunteers and two studies in patients with schizophrenia. Data from a comparative bioavailability study in medically stable patients and a Phase III study in patients with acute exacerbation of schizophrenia were then incorporated, using empirical Bayesian feedback and model refinement in NONMEM. Finally, covariate analysis was performed on CL40. RESULTS: The final model adequately described the pharmacokinetics of 6288 active moiety concentrations in 17 healthy volunteers and 430 patients with schizophrenia. This one-compartment disposition model had a complex absorption process, combining a small amount immediately entering the central active moiety compartment, two first-order absorption processes and a combined zero-order and first order process, with first-order elimination from the central compartment. Significant covariates on CL40 were BMI and sex. Goodness-of-fit (GOF) plots and visual predictive checks (VPC) confirmed acceptable description of the data. CONCLUSIONS: The population PK model adequately described active moiety concentrations from five clinical studies after risperidone ISM® administration. Relationships between active moiety exposure and covariates were defined in order to facilitate simulations for future studies. The model showed that risperidone ISM® rapidly achieves therapeutic plasma levels within the first hours after the first injection that are maintained sustainedly throughout the whole dosing interval following once-monthly gluteal injections of 100 mg and 75 mg.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

Non-invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response.

BACKGROUND AND AIMS: A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR). METHODS: The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package). RESULTS: Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%. CONCLUSIONS: A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.

The earliest maize from San Marcos Tehuacán is a partial domesticate with genomic evidence of inbreeding.

Pioneering archaeological expeditions lead by Richard MacNeish in the 1960s identified the valley of Tehuacán as an important center of early Mesoamerican agriculture, providing by far the widest collection of ancient crop remains, including maize. In 2012, a new exploration of San Marcos cave (Tehuacán, Mexico) yielded nonmanipulated maize specimens dating at a similar age of 5,300-4,970 calibrated y B.P. On the basis of shotgun sequencing and genomic comparisons to Balsas teosinte and modern maize, we show herein that the earliest maize from San Marcos cave was a partial domesticate diverging from the landraces and containing ancestral allelic variants that are absent from extant maize populations. Whereas some domestication loci, such as teosinte branched1 (tb1) and brittle endosperm2 (bt2), had already lost most of the nucleotide variability present in Balsas teosinte, others, such as teosinte glume architecture1 (tga1) and sugary1 (su1), conserved partial levels of nucleotide variability that are absent from extant maize. Genetic comparisons among three temporally convergent samples revealed that they were homozygous and identical by descent across their genome. Our results indicate that the earliest maize from San Marcos was already inbred, opening the possibility for Tehuacán maize cultivation evolving from reduced founder populations of isolated and perhaps self-pollinated individuals.

Severe obscure gastrointestinal bleeding successfully treated with idarucizumab.

Idarucizumab is a monoclonal antibody that rapidly reverses the anticoagulant effect of dabigatran. The experience with this drug in the setting of gastrointestinal bleeding is scarce. We present the case of an 84-year-old male with known history of non-valvular atrial fibrillation anticoagulated with dabigatran who presented to the emergency room with melena. During his stay in the emergency department he suddenly worsened with hemodynamic derangement and massive melena so idarucizumab was administered. Gastroscopy and colonoscopy were performed without identifying a bleeding source. After the administration of idarucizumab, the patient did not presented signs of ongoing bleeding. Anticoagulation was resumed on the sixth day and no rebleeding or thromboembolic events have been recorded after six months of follow-up. This case and the limited information available in the literature suggest that idarucizumab can be useful and safe in cases of severe gastrointestinal bleeding with recent intake of dabigatran.

[Acute liver ischaemia after gastro-oesophageal variceal bleeding]. / Isquemia hepática aguda tras hemorragia digestiva alta por varices esofagogástricas.

INTRODUCTION: Variceal upper gastrointestinal bleeding (UGIB) can trigger acute hypoxic hepatitis (AHH). The aim of this study was to analyse the incidence, associated risk factors and mortality of AHH after variceal UGIB. PATIENTS AND METHODS: Retrospective study of cirrhotic patients with variceal UGIB, classified into 2 groups according to the development of AHH. AHH was diagnosed when AST and ALT reached levels 10 times above the upper limit of normal, after ruling out other causes of hepatitis. The standard initial treatment consisted of haemodynamic support, emergency endoscopy with rubber band ligation, somatostatin and antibiotics. In the case of failure of primary haemostasis, a transjugular intrahepatic portosystemic shunt (TIPS) was implanted. Both groups (AHH and non-AHH) were compared. RESULTS: Sixty-eight cirrhotic patients with variceal UGIB admitted to the gastroenterology department of Hospital Ramón y Cajal between January 2007 and March 2012 were analysed. Eleven of these patients (16.2%) developed AHH. Univariate analysis showed the following items as risk factors: diabetes (OR: 7.5; CI: 1.9-29), shock (OR: 8.5; CI: 2.06-34) and persistent bleeding (OR: 9.0, CI: 1.6-49, P=.03). However, multivariate analysis confirmed only diabetes (OR: 8.61; CI: 1.4-52.5) and shock (OR: 7.58; CI: 1.26-45.51) as risk factors. Mortality rate in the AHH group was 45%, compared to 10.5% in the non-HAA group (P=.012). CONCLUSIONS: AHH after variceal UGIB occurred in 16.2% of cirrhotic patients and was associated with a poorer prognosis, with a mortality rate of 45%. Our findings suggest that diabetes and shock are risk factors for the development of AHH. Early identification of at-risk patients could therefore help prevent AHH.

[An infrequent cause of iron-deficiency anemia: Ménétrier disease]. / Una causa infrecuente de anemia ferropénica: Enfermedad de Ménétrier.

Ménétrier disease is a rare condition of an unknown origin, with a wide spectrum of clinical signs and symptoms at presentation. Diagnosis is made through the combination of clinical, analytical, endoscopic and histological data. Surgery is the classical treatment. However, new medical approaches have emerged.

[Capsule endoscopy and obscure gastrointestinal bleeding: does the form of presentation matter?]. / Cápsula endoscópica y hemorragia digestiva de origen oscuro: ¿importa la forma de presentación?

INTRODUCTION: Obscure gastrointestinal bleeding (OGIB) is defined as bleeding from the gastrointestinal tract with no obvious cause after assessment with upper and lower gastrointestinal endoscopy. In these cases, the source is suspected to be in the small bowel. Obscure bleeding can be occult or overt. The aim of this study was to analyze the clinical and analytical characteristics and findings on capsule endoscopy in patients with OGIB and to determine the factors related to the detection of lesions in both forms of presentation. METHODS: We performed a retrospective study of capsule endoscopies carried out between November 2009 and November 2012 for OGIB. RESULTS: We analyzed 284 capsule endoscopies in 272 patients. Initially, 12 procedures could not be evaluated and were repeated. A total of 272 procedures were finally included in the analysis. The results of 114 (41.9%) capsule endoscopies were normal. Compared with patients with occult OGIB, those with overt OGIB were significantly older (70.2 vs. 67.5 years; p = 0.04), consumed more NSAID (24.2% vs. 11.9%; p = 0.01), had higher hemoglobin levels (9.3 vs. 10.4; p < 0,001) and more frequently required transfusion (64.5% vs 32.2%; p < 0.001). No differences were found between the two forms of presentation in the detection of canker sores-ulcers and polyps-masses. Vascular lesions were more frequently detected in overt than in occult OGIB (40.3% vs. 25.7%, respectively), (p < 0.05). When the total number of diagnoses carried out by capsule endoscopy was analyzed, no differences were found in diagnostic yield between overt OGIB (57%) and occult OGIB (54%), (p = 0.6). In overt OGIB, multivariate analysis showed that the variables that significantly predicted the detection of lesions on capsule endoscopy were consumption of medication NSAID (OR 2.75; p = 0.01), antiplatelets and anticoagulants (OR 2.64; p = 0.03) and analytical data hemoglobin (OR 3.23; p < 0.001) and INR (OR 1.8; p = 0.02). In occult OGIB, multivariate analysis showed that the factors significantly related to the detection of lesions on endoscopy were age (OR 1.9; p = 0.04) and NSAID consumption (OR 2.1; p = 0.01). CONCLUSIONS: Capsule endoscopy is essential in the assessment of OGIB. Although the diagnostic yield was similar in both forms of presentation, vascular lesions were more frequently detected in overt OGIB. The diagnostic yield of capsule endoscopy could be optimized by taking into account the form of presentation (overt vs. occult) and certain clinical and analytic data (age, drug consumption, hemoglobin).

Hyponatremia influences the outcome of patients with acute-on-chronic liver failure: an analysis of the CANONIC study.

INTRODUCTION: Hyponatremia is a marker of poor prognosis in patients with cirrhosis. This analysis aimed to assess if hyponatremia also has prognostic value in patients with acute-on-chronic liver failure (ACLF), a syndrome characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. METHODS: We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,341 consecutive patients admitted to 29 European centers with acute decompensation of cirrhosis (including ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infections, or any combination of these), both with and without associated ACLF (301 and 1,040 respectively). RESULTS: Of the 301 patients with ACLF, 24.3% had hyponatremia at inclusion compared to 12.3% of 1,040 patients without ACLF (P <0.001). Model for end-stage liver disease, Child-Pugh and chronic liver failure-SOFA scores were significantly higher in patients with ACLF and hyponatremia compared to those without hyponatremia. The presence of hyponatremia (at inclusion or during hospitalization) was a predictive factor of survival both in patients with and without ACLF. The presence of hyponatremia and ACLF was found to have an independent effect on 90-day survival after adjusting for the potential confounders. Hyponatremia in non-ACLF patients nearly doubled the risk (hazard ratio (HR) 1.81 (1.33 to 2.47)) of dying at 90 days. However, when considering patients with both factors (ACLF and hyponatremia) the relative risk of dying at 90 days was significantly higher (HR 6.85 (3.85 to 12.19) than for patients without both factors. Patients with hyponatremia and ACLF had a three-month transplant-free survival of only 35.8% compared to 58.7% in those with ACLF without hyponatremia (P <0.001). CONCLUSIONS: The presence of hyponatremia is an independent predictive factor of survival in patients with ACLF. In cirrhosis, outcome of patients with ACLF is dependent on its association with hyponatremia.

Survey on the Situation of Medical Departments in the Pharmaceutical Industry in Spain.

INTRODUCTION: Medical departments have evolved from a position of support to one of strategic leadership. The number of tasks and the complexity of interactions in which they are involved is increasing. However, the spectrum of their activity in the sector differs significantly from one company to another. Therefore, the aim of this study was to describe their situation within the pharmaceutical industry, analyzing the positions, functions, and profiles of their professionals. METHODS: This study consisted of an online survey containing 25 questions grouped into four blocks (structure, medical direction, training, and activities and responsibilities). Medical departments in the Spanish pharmaceutical industry of different sizes and scope were invited to participate. The survey took place in 2021, with a designated response period of three months. It is important to note that all responses collected during this time were treated as anonymous. RESULTS: Thirty companies participated. A total of 93.3% of respondents worked for an international laboratory, with a size of 0-5 or 11-20 people (20.7%). For 27.6% of the companies, the number of medical advisors per medical department was 1 or 4, with varying numbers of medical scientific liaisons (1, 6-10, and > 20). A total of 56.7%, 33.3%, and 6.7% indicated that the country manager, head of regional medical affairs, and head of global medical affairs, respectively, had a solid-line reporting relationship with the medical directorate. Medical directors were mostly graduates in medicine (86.2%) with a doctorate (34.5%), and medical managers were mainly graduates in medicine (77.8%) and pharmacy (66.7%). CONCLUSIONS: This study reveals that respondents predominantly work in internationally focused laboratories, with professionals ranging from experienced medical directors to managers with 6-20 years of experience, each with distinct roles.

[Rescue therapy with sulfasalazine prior to immunosuppressive or biological agents in ulcerative colitis poorly controlled with mesalazine]. / Rescate con sulfasalazina antes de inmunosupresores o agentes biológicos en la colitis ulcerosa mal controlada con mesalazina.

INTRODUCTION: In ulcerative colitis, aminosalicylates are the mainstay of maintenance therapy. Sulfasalazine was the first aminosalicylic used in the maintenance therapy of this disease. Later, mesalazine was preferred due to its supposedly better tolerability. However, recent studies indicate certain benefits of the use of sulfasalazine because of its possible superior effectiveness. The aim of this study was to determine whether patients with ulcerative colitis poorly controlled by mesalazine as maintenance therapy respond to sulfasalazine, thus avoiding the use of immunosuppressive or biological therapies. METHODS: The Inflammatory Bowel Disease Clinic of the Ramón y Cajal Hospital maintains a database in which all drug exposures are registered. We selected patients poorly controlled with mesalazine who had received sulfasalazine as rescue maintenance therapy. We determined the percentage of patients poorly controlled with mesalazine who responded to sulfasalazine. RESULTS: Of 415 patients with ulcerative colitis, 49 had been treated with sulfasalazine at some time. Of these, sulfasalazine was selected as an alternative therapy due to poor disease control with mesalazine. The median duration of mesalazine therapy until the switch was 20.8 months, with a median dose of 3.35 g/day. In 21 of the 31 patients (67.7%), sulfasalazine was able to control symptoms and maintain remission. CONCLUSION: Despite the limitations of this study, we found that 67.7% of patients with ulcerative colitis poorly controlled with mesalazine responded to a switch to sulfasalazine. These patients would normally have progressed to immunosuppressive, biological or surgical treatments. This option merits further studies. Meanwhile sulfasalazine should not be forgotten in the management of ulcerative colitis.

Sequences of Alterations in Inflammation and Autophagy Processes in Rd1 Mice.

(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.

[Octreotide treatment for postoperative chylous ascites in an adult]. / Ascitis quilosa posquirúrgica en un adulto tratada con octreótida.

Chylous ascites is infequent after abdominal surgery. We describe the case of a 43-year-old man with portal cavernomatosis who underwent surgery to insert a splenorenal shunt, which was not placed due to the absence of signs of portal hypertension. On postoperative day 20, the patient developed abdominal distension and mild dyspnea and was diagnosed with chylous ascites, which was related to the surgery. The patient was initially treated with diet and diuretics, with no clinical response, and consequently octreotide therapy was started. Four days later, the ascites was almost resolved and an ultrasound scan at 4 months showed its complete disappearance. This article demonstrates the effectiveness of octreotide in the treatment of postsurgical chylous ascites.

[An exceptional cause of acute hepatitis in an adult: parvovirus B19]. / Una causa excepcional de hepatitis aguda en el adulto: parvovirus B19.

There are multiple causes of hepatitis. The most frequent etiologies are viral, usually hepatitis A, B and C viruses. However, other, non-hepatotropic viruses can cause this disease, including parvovirus B19. We present a case of acute hepatitis due to parvovirus B19, as well as a review of the epidemiological, clinical, diagnostic and therapeutic features of this entity.

Sulforaphane Modulates the Inflammation and Delays Neurodegeneration on a Retinitis Pigmentosa Mice Model.

The term retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. From a cellular view, retinal degeneration is prompted by an initial death of rods, followed later by cone degeneration. This cellular progressive degeneration is translated clinically in tunnel vision, which evolves to complete blindness. The mechanism underlying the photoreceptor degeneration is unknown, but several mechanisms have been pointed out as main co-stars, inflammation being one of the most relevant. Retinal inflammation is characterized by proliferation, migration, and morphological changes in glial cells, in both microglia and Müller cells, as well as the increase in the expression of inflammatory mediators. Retinal inflammation has been reported in several animal models and clinical cases of RP, but the specific role that inflammation plays in the pathology evolution remains uncertain. Sulforaphane (SFN) is an antioxidant natural compound that has shown anti-inflammatory properties, including the modulation of glial cells activation. The present work explores the effects of SFN on retinal degeneration and inflammation, analyzing the modulation of glial cells in the RP rd10 mice model. A daily dose of 20 mg/kg of sulforaphane was administered intraperitoneally to control (C57BL/6J wild type) and rd10 (Pde6brd10) mice, from postnatal day 14 to day 20. On postnatal day 21, euthanasia was performed. Histological retina samples were used to assess cellular degeneration, Müller cells, and microglia activation. SFN administration delayed the loss of photoreceptors. It also ameliorated the characteristic reactive gliosis, assessed by retinal GFAP expression. Moreover, sulforaphane treatment regulated the microglia activation state, inducing changes in the microglia morphology, migration, and expression through the retina. In addition, SFN modulated the expression of the interleukins 1ß, 4, Ym1, and arginase inflammatory mediators. Surprisingly, M2 polarization marker expression was increased at P21 and was reduced by SFN treatment. To summarize, SFN administration reduced retinal neurodegeneration and modified the inflammatory profile of RP, which may contribute to the SFN neuroprotective effect.

Time-Course Changes in Oxidative Stress and Inflammation in the Retinas of rds Mice: A Retinitis Pigmentosa Model.

(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.