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Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1β, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1β gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR. [ABSTRACT FROM AUTHOR]

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods. [ABSTRACT FROM AUTHOR]

Choroideremia, an incurable, progressive retinal degeneration primarily affecting young men, leads to sight loss. GEMINI was a multicenter, open-label, prospective, two-period, interventional Phase II study assessing the safety of bilateral sequential administration of timrepigene emparvovec, a gene therapy, in adult males with genetically confirmed choroideremia (NCT03507686, ClinicalTrials.gov). Timrepigene emparvovec is an adeno-associated virus serotype 2 vector encoding the cDNA of Rab escort protein 1, augmented by a downstream woodchuck hepatitis virus post-transcriptional regulatory element. Up to 0.1 mL of timrepigene emparvovec, containing 1 × 1011 vector genomes, was administered by subretinal injection following vitrectomy and retinal detachment. The second eye was treated after an intrasurgery window of <6, 6–12, or >12 months. Each eye was followed at up to nine visits over 12 months. Overall, 66 participants received timrepigene emparvovec, and 53 completed the study. Visual acuity (VA) was generally maintained in both eyes, independent of intrasurgery window duration, even after bilateral retinal detachment and subretinal injection. Bilateral treatment was well tolerated, with predominantly mild or moderate treatment-emergent adverse events (TEAEs) and a low rate of serious surgical complications (7.6%). Retinal inflammation TEAEs were reported in 45.5% of participants, with similar rates in both eyes; post hoc analyses found that these were not associated with clinically significant vision loss at month 12 versus baseline. Two participants (3.0%) reported serious noninfective retinitis. Prior timrepigene emparvovec exposure did not increase the risk of serious TEAEs or serious ocular TEAEs upon injection of the second eye; furthermore, no systemic immune reaction or inoculation effect was observed. Presence of antivector neutralizing antibodies at baseline was potentially associated with a higher percentage of TEAEs related to ocular inflammation or reduced VA after injection of the first eye. The GEMINI study results may inform decisions regarding bilateral sequential administration of other gene therapies for retinal diseases. [ABSTRACT FROM AUTHOR]

Introduction: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. Methods: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. Results: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. Conclusions: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients. Here we investigate a novel target for AMD. Granzyme B (GzmB) is a serine protease that promotes aging, chronic inflammation and vascular permeability through the degradation of the extracellular matrix (ECM) and tight junctions. Extracellular GzmB is increased in retina pigment epithelium (RPE) and mast cells in the choroid of the healthy aging outer retina. It is further increased in donor eyes exhibiting features of nAMD and CNV. Here, we show in RPE-choroidal explant cultures that exogenous GzmB degrades the RPE-choroid ECM, promotes retinal/choroidal inflammation and angiogenesis while diminishing anti-angiogenic factor, thrombospondin-1 (TSP-1). The pharmacological inhibition of either GzmB or mast-cell degranulation significantly reduces choroidal angiogenesis. In line with our in vitro data, GzmB-deficiency reduces the extent of laser-induced CNV lesions and the age-related deterioration of electroretinogram (ERG) responses in mice. These findings suggest that targeting GzmB, a serine protease with no known endogenous inhibitors, may be a potential novel therapeutic approach to suppress CNV in nAMD. [ABSTRACT FROM AUTHOR]

Background and Objective: Outer retinal tubulation (ORT) is observed on optical coherence tomography images from patients with geographic atrophy (GA), but its clinical implications are unclear. The objective of this study was to investigate the prevalence of ORT and its association with GA lesion growth rates. Materials and Methods: This post hoc longitudinal analysis assessed 62 eyes randomized to sham treatment in the phase 2 FILLY trial. ORT prevalence was estimated at baseline, month 12, and month 18 and change in GA lesion growth from baseline to month 18 was calculated. Results: ORT prevalence rates were 24%, 43%, and 43% at baseline, month 12, and month 18, respectively. Slower mean GA lesion growth was observed in eyes with ORT present at baseline in the overall population as well as the subfoveal and nonsubfoveal GA subgroups. Conclusion: ORT presence may indicate a slower-growing GA lesion phenotype, independent of foveal involvement. [Ophthalmic Surg Lasers Imaging Retina 2024;55:448–451.] [ABSTRACT FROM AUTHOR]

This report describes a unique case of a Coats-like presentation of familial exudative vitreoretinopathy in an 11-year-old girl. The patient was originally referred for evaluation of presumed Coats disease and presented with telangiectatic vessels, perivascular exudates, diffuse peripheral exudation, and intraretinal hemorrhages. Clinical and angiographical findings were consistent with familial exudative vitreoretinopathy, while genetic testing identified variants of uncertain significance in two associated genes, LRP5 and ZNF408. In silico analysis predicts the LRP5 variant to be pathogenic. Retinal vasculopathies often have phenotypic overlap, warranting angiographic examination of both eyes and genetic testing to uncover the correct diagnosis and guide proper treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:462–466.] [ABSTRACT FROM AUTHOR]

Introduction: Central Serous Chorioretinopathy (CSC), a leading cause of vision loss, presents diverse treatment challenges based on its acute or chronic manifestation. Areas covered: In acute CSC, treatment typically involves observation, reserving intervention for cases where optimal vision is crucial for professional activities. Emerging evidence advocates the use of half-dose or half-fluence Photodynamic Therapy (PDT), directed by Indocyanine Green Angiography (ICGA) or Fluorescein Angiography (FA), to hasten subretinal fluid (SRF) resolution, improve vision, and minimize recurrence. Chronic CSC, on the other hand, increasingly favors half-dose PDT, a recommendation strengthened by studies such as the PLACE trial. CSC complicated by Choroidal Neovascularization (CNV) necessitates management through intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) injections and/or half-dose PDT. In cases of polypoidal choroidal vasculopathy (PCV), a combination of anti-VEGF therapy with PDT proves beneficial. For scenarios where standard treatments are impractical, Eplerenone emerges as the primary oral medication. Methods: A literature search of all original articles was performed using the major online databases. The following keywords 'Central Serous Chorioretinopathy' and 'Treatment,' were searched in combination with 'Photodynamic therapy,' 'Focal Laser Photocoagulation,' 'Subthreshold Micropulse Laser' and 'Systemic treatments.' Expert opinion: Managing CSC requires a patient-centered approach. In acute CSC, careful monitoring and lifestyle modifications may suffice, while in chronic CSC, PDT is a primary therapeutic option. [ABSTRACT FROM AUTHOR]

Image segmentation is a crucial task in computer vision and image processing, with numerous segmentation algorithms being found in the literature. It has important applications in scene understanding, medical image analysis, robotic perception, video surveillance, augmented reality, image compression, among others. In light of this, the widespread popularity of deep learning (DL) and machine learning has inspired the creation of fresh methods for segmenting images using DL and ML models respectively. We offer a thorough analysis of this recent literature, encompassing the range of ground-breaking initiatives in semantic and instance segmentation, including convolutional pixel-labeling networks, encoder-decoder architectures, multi-scale and pyramid-based methods, recurrent networks, visual attention models, and generative models in adversarial settings. We study the connections, benefits, and importance of various DL- and ML-based segmentation models; look at the most popular datasets; and evaluate results in this Literature. [ABSTRACT FROM AUTHOR]

Branch retinal vein occlusion (BRVO) is the most prevalent retinal vascular disease that constitutes a threat to vision due to increased venous pressure caused by venous effluent in the space, leading to impaired visual function. Optical Coherence Tomography Angiography (OCTA) is an innovative non-invasive technique that offers high-resolution three-dimensional structures of retinal blood vessels. Most publicly available datasets are collected from single visits with different patients, encompassing various eye diseases for distinct tasks and areas. Moreover, due to the intricate nature of eye structure, professional labeling not only relies on the expertise of doctors but also demands considerable time and effort. Therefore, we have developed a BRVO-focused dataset named Soul (Source of ocular vascular) and propose a human machine collaborative annotation framework (HMCAF) using scrambled retinal blood vessels data. Soul is categorized into 6 subsets based on injection frequency and follow-up duration. The dataset comprises original images, corresponding blood vessel labels, and clinical text information sheets which can be effectively utilized when combined with machine learning. [ABSTRACT FROM AUTHOR]

Introduction: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO). Methods: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product. Results: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study. Conclusions: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease. Trial Registration: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12. [ABSTRACT FROM AUTHOR]

Introduction: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. Methods: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. Results: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. Conclusions: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15. [ABSTRACT FROM AUTHOR]

Neurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber's hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients' serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson's, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30–P90, and dopamine levels were 25–35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Peripapillary vitreous traction (PVT) occurring without any underlying eye disease has been contemplated as a distinct entity from nonarteritic ischemic optic neuropathy (NAION) for many years and is sometimes difficult to differentiate from classical NAION. We report 6 new cases to analyze the clinical features of PVT syndrome that would expand the clinical spectrum of anterior optic neuropathies. METHODS: Prospective case series. RESULTS: PVT syndrome seems to affect optic discs with a small area with a small cup-to-disc (C/D) ratio. The C/D ratio does not significantly increase in the chronic stage, as in NAION. Vitreous traction without detachment can either lead to mild retinal nerve fiber layer (RNFL) injury with attendant ganglion cell layer/inner plexiform layer (GCL/IPL) thinning in 29% or no injury at all in 71%. Eighty-six percent had good visual acuity (VA) and had no relative afferent pupillary defect (RAPD), whereas 14% had a transient RAPD; 71% had no color defect. Vitreous detachment after a period of severe and persistent traction can lead to more damage to the optic nerve head and RNFL that may look like NAION. Our hypothesized mechanically induced injury to the superficial optic nerve head may not lead to much visual impairment. In our study, no further therapeutic interventions were required. CONCLUSIONS: Based on our analysis of previously published cases and our own prospective case series of 6 patients, the PVT syndrome falls within the spectrum of anterior optic neuropathies, often affecting small optic discs with a small C/D ratio. Vitreous traction can lead to a partial or complete anterior optic neuropathy. The PVT syndrome may be a more anterior optic neuropathy distinct from classical NAION.

Abstract Purpose This scoping review aims to explore the current applications of ChatGPT in the retina field, highlighting its potential, challenges, and limitations. Methods A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, MEDLINE, and Embase, to identify relevant articles published from 2022 onwards. The inclusion criteria focused on studies evaluating the use of ChatGPT in retinal healthcare. Data were extracted and synthesized to map the scope of ChatGPT’s applications in retinal care, categorizing articles into various practical application areas such as academic research, charting, coding, diagnosis, disease management, and patient counseling. Results A total of 68 articles were included in the review, distributed across several categories: 8 related to academics and research, 5 to charting, 1 to coding and billing, 44 to diagnosis, 49 to disease management, 2 to literature consulting, 23 to medical education, and 33 to patient counseling. Many articles were classified into multiple categories due to overlapping topics. The findings indicate that while ChatGPT shows significant promise in areas such as medical education and diagnostic support, concerns regarding accuracy, reliability, and the potential for misinformation remain prevalent. Conclusion ChatGPT offers substantial potential in advancing retinal healthcare by supporting clinical decision-making, enhancing patient education, and automating administrative tasks. However, its current limitations, particularly in clinical accuracy and the risk of generating misinformation, necessitate cautious integration into practice, with continuous oversight from healthcare professionals. Future developments should focus on improving accuracy, incorporating up-to-date medical guidelines, and minimizing the risks associated with AI-driven healthcare tools.

The review discusses the current state of affairs and prospects for the use of virtual reality (VR) technologies in visual rehabilitation strategies based on neuroplasticity activation. Vision training in VR has a number of advantages compared to traditional rehabilitation activities. Play-based VR exercises, practices in a safe and controlled environment, attract the users and encourage them to actively participate in therapy and comply with the treatment plan. VR systems have options that enable the creation of individual treatment programs tailored to the specific needs and abilities of each patient. VR systems are only beginning to be used in the rehabilitation of visually impaired but on the whole show promising results already. Yet, more careful evaluation of the results and additional research are required to overcome the existing limitations of the approach, such as a small size of the sample and lack of control groups. Objective diagnostic methods are needed to create a solid and high-quality evidence base. It seems promising to expand the potentials of VR technologies for visual rehabilitation of diverse retinal pathology patients by combining visual training in the virtual world with rhythmic photostimulation using optimal parameters of optical signals.

Abstract Objectives To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera. Methods Systematic literature reviews were conducted to determine the long-term (≥ 18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion). Results Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0–5.0%) of study eyes in clinical trials and 1.3% (0.0–14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0–22.8%) and 2.2% (0.9–4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants. Conclusions The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice. Trial Registration PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129.

Regular physical exercise is known to lower the incidence of age-related eye diseases. We aimed to assess the acute chorioretinal alterations in older adults following intense physical strain. Seventeen senior elite athletes were recruited who underwent an aerobic exercise on a cycle ergometer and macular scanning by optical coherence tomography. A significant thinning of the entire retina was observed 1 min after exercise, followed by a thickening at 5 min, after which the thickness returned to baseline. This trend was similar in almost every single retinal layer, although a significant change was observed only in the inner retina. Choroidal thickness changes were neither significant nor did they correlate with the thickness changes of intraretinal layers. The mechanism of how these immediate retinal changes chronically impact age-related sight-threatening pathologies that, in turn, result in a substantially reduced quality of life warrants further investigation on nontrained older adults as well. [ABSTRACT FROM AUTHOR]

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues. Pyrroloquinoline quinone is present in the diet being available in foodstuffs, conferring the potential of this compound to be supplemented by dietary administration. Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction, growth, and immunity resulting from the dietary absence of pyrroloquinoline quinone, and as such, pyrroloquinoline quinone has been considered as a “new vitamin.” Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established, the wide range of benefits for health provided has been reported in many studies. In this respect, pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts, thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life. Through the regulation of different metabolic mechanisms, pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death. Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration, although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated. Here, we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts. In addition, we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.