Sexual Minorities and Loneliness: Exploring Sexuality through Social Media and Gender-Sexuality Alliance (GSA) Supports.

We examined online and offline social supports for sexual minority adolescents, underscoring the understudied developmental period of early adolescence and the mental outcome of loneliness. Stemming from a larger study in the northeast U.S., 967 youth participants were 26% sexual minority, 53% female, 45% male, and 2% other/nonbinary (mean age = 13.1, SD = 1.52). LGBTQ+ youth reported significantly higher levels of loneliness compared to their heterosexual counterparts. To understand potential sources of social support while exploring their sexual identities, we compared the experiences of LGBTQ+ youth at both ends of the loneliness spectrum. Gaining knowledge about their sexual orientation from LGBTQ+ organization websites, participating in gender-sexuality alliances, and using TikTok or Instagram were associated with lower levels of loneliness. Providing social support to online friends was associated with lower loneliness; however, receiving online support was not associated with lower loneliness. Furthermore, proactive social media engagement such as posting uplifting content, joining online communities, or raising awareness about social issues were associated with lower levels of loneliness. The results provide guidance on specific youth behaviors and online communities beyond a focus on screen time while highlighting the continued need for social support to ameliorate loneliness, such as gender-sexuality alliance networks.

LED-based characterization of solar cells for underwater applications.

Improved solar energy harvesting in aquatic environments would allow for superior environmental monitoring. However, developing underwater solar cells is challenging as evaluation typically requires deployment in the field or in large water tanks that can simulate aquatic light conditions. Here, we present a protocol to test underwater solar cells using a light-emitting diode (LED)-based characterization technique usable in a typical laboratory setting. We describe steps for installing and running Python code, matching LEDs to irradiance, characterizing underwater solar cells, and calculating underwater solar cell efficiency. For complete details on the use and execution of this protocol, please refer to Röhr et al.1.

Predicting adolescent suicidal behavior following inpatient discharge using structured and unstructured data.

BACKGROUND: The objective was to develop and assess performance of an algorithm predicting suicide-related ICD codes within three months of psychiatric discharge. METHODS: This prognostic study used a retrospective cohort of EHR data from 2789 youth (12 to 20 years old) hospitalized in a safety net institution in the Northeastern United States. The dataset combined structured data with unstructured data obtained through natural language processing of clinical notes. Machine learning approaches compared gradient boosting to random forest analyses. RESULTS: Area under the ROC and precision-recall curve were 0.88 and 0.17, respectively, for the final Gradient Boosting model. The cutoff point of the model-generated predicted probabilities of suicide that optimally classified the individual as high risk or not was 0.009. When applying the chosen cutoff (0.009) to the hold-out testing set, the model correctly identified 8 positive cases out of 10, and 418 negative cases out 548. The corresponding performance metrics showed 80 % sensitivity, 76 % specificity, 6 % PPV, 99 % NPV, F-1 score of 0.11, and an accuracy of 76 %. LIMITATIONS: The data in this study comes from a single health system, possibly introducing bias in the model's algorithm. Thus, the model may have underestimated the incidence of suicidal behavior in the study population. Further research should include multiple system EHRs. CONCLUSIONS: These performance metrics suggest a benefit to including both unstructured and structured data in design of predictive algorithms for suicidal behavior, which can be integrated into psychiatric services to help assess risk.

Offering recovery rather than punishment: Implementation of a law enforcement-led pre-arrest diversion-to-treatment program for adults with substance use disorders.

BACKGROUND: The opioid epidemic has strained the US criminal justice system. Law enforcement frequently encounters persons with substance use disorder (SUD). Law enforcement-led, pre-arrest diversion programs linking individuals with SUD to addiction treatment instead of arrest and prosecution has the potential to reduce crime, overdoses, and other community harms. We implemented a pre-arrest diversion-to-treatment program-the Madison Addiction Recovery Initiative (MARI)-from September 2017 to August 2020, and describe the key components of MARI's effective implementation. METHODS: Adults who committed an eligible, drug use-related crime were offered a 6-month MARI participation with referral to treatment in lieu of arrest; criminal charges for that crime were "voided" upon the successful MARI completion. Formative evaluation, with stakeholder feedback and team meeting minutes, assessed key factors influencing implementation. Process evaluation consisted of tracking participant referrals, enrollment, and engagement. Police officers, MARI participants, and treatment center staff members were surveyed about program experiences and attitudes. The study used descriptive statistics to describe quantitative survey responses; thematic qualitative analysis identified major themes in qualitative responses. RESULTS: Of 263 participants, 160 initiated program engagement, with 100 successfully completing MARI. Interim evaluations and community partner feedback informed program protocol adjustments to increase participant enrollment, retention and diversity, streamline the referral processes, and transition to telehealth during the COVID-19 pandemic. CONCLUSION: Rigorous evaluation and community partner feedback are essential components of effective implementation and sustainability of a law enforcement-led pre-arrest diversion-to-treatment program, which has the potential to both reduce crime and overdose, and change the lives of people with SUD.

Longitudinal trends in liquid laundry detergent packet exposures: 2014-2022.

BACKGROUND: Liquid laundry detergent packet exposures modestly declined in the mid-2010s among children less than 6 years of age due to public awareness and voluntary product safety standards. We aimed to assess longitudinal trends in the number and rate of liquid laundry detergent packet exposures in the United States by age. METHODS: Data from the National Poison Data System were analyzed to characterize liquid laundry detergent packet exposures between January 2014 and December 2022. RESULTS: From 2014-2022, there were 114,826 single and polysubstance exposures to liquid laundry detergent packets. Children less than 6 years of age (86.8 percent) were most commonly exposed. When evaluating multi-year trends, we found that the annual exposure rate per 1 million children less than 6 years old increased by 16.8 percent from 392.6 in 2018 to 458.7 in 2020. Subsequently, the annual exposure rate in children less than 6 years of age declined by 6.8 percent from 2020 to 2022 (427.4 exposures per 1 million). The annual rate of adolescent exposures increased by 85.4 percent from 2014 (4.1 exposures per 1 million) to 2017 (7.6 exposures per 1 million), with a subsequent increase of 155.3 percent from 2017 to 2018 (19.4 exposures per 1 million). Among adults, the annual exposure rate increased by 147.1 percent from 2014 (1.7 exposures per 1 million) to 2022 (4.2 exposures per 1 million). The number of more serious medical outcomes and hospital admissions among children less than 6 years of age declined by 44.3 percent and 68.6 percent, respectively, between 2014 and 2018. CONCLUSIONS: Despite declines in the number, rate, and severity of liquid laundry detergent packet exposures among children less than 6 years old, the exposure burden remains high. Additionally, exposures have increased among older children, adolescents, and adults. Renewed safety efforts are warranted to protect prior public health gains and further reduce exposures.

A Review of the Efficacy of Topical Statins for Treating Disseminated Superficial Actinic Porokeratosis.

Porokeratosis is a rare group of acquired or hereditary dermatoses characterized by linear or annular plaques with a keratotic border. DSAP is the most common porokeratosis, and lesions range from asymptomatic to pruritic circular pink to brown macules, papules, or plaques surrounded by a raised border. DSAP carries about 7.5-10% risk of malignant transformation to SCC or BCC. While in the past DSAP has been widely treated with topical diclofenac, ingenol mebutate, topical vitamin D analog, 5-fluorouracil, imiquimod, photodynamic therapy, retinoids, cryotherapy, and laser therapy, these therapies have shown limited efficacy and have caused adverse effects including inflammatory reactions, hyperpigmentation, pain, and erythema. Recently, a formulation of topical statin and cholesterol has surfaced as a new and promising treatment for DSAP which has shown clinical improvement with a tolerable adverse effect profile when compared to the current therapies. Of the 8 case studies with a total of 20 patients with DSAP, 90% (18/20) reported clinical improvement with various forms of topical statin therapy. While promising, larger randomized controlled trials are needed to evaluate the long-term use of topical statins for DSAP. J Drugs Dermatol. 2023;22(10):     doi:10.36849/JDD.7540.

Clinical Outcome of Amniotic Membrane Transplant in Ocular Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis at a Major Burn Unit.

PURPOSE: To analyze the clinical outcome of amniotic membrane transplantation in patients with ocular Stevens-Johnson syndrome/toxic epidermal necrolysis at a major burn unit. DESIGN: Retrospective, non-randomized interventional study. METHODS: A retrospective chart review from April 2014 to January 2022 of 43 patients (85 eyes) at a burn center who underwent amniotic membrane transplantation (AMT) for severe ocular Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN was performed. Data regarding the clinical course and outcome were obtained. A comparison between the use of cryopreserved AMT rings (cryoAMT) and dehydrated AMT (deAMT) was also assessed. RESULTS: A total of 85 eyes in 43 patients underwent AMT for severe ocular SJS/TEN. Of the eyes, 72 received deAMT with symblepharon ring, whereas 13 received cryoAMT over the cornea surface. All patients had deAMT placed over the eyelid margins and palpebral conjunctivae and tucked into the fornices. The average best-corrected visual acuity (BCVA) on last follow-up examination was 20/33, 20/30, and 20/34 in all eyes, the cryoAMT group, and the deAMT group, respectively (no significant difference between groups). The most common suspected inciting agent was lamotrigine (17% of all cases). The average long-term complication score was 1.4, with no significant difference between the cryoAMT group (1.6) and the deAMT group (1.4, P = .5). Symblepharon formation was seen more in the cryoAMT group compared to the deAMT group (P < .05). CONCLUSION: The use of AMTs in severe ocular SJS/TEN greatly mitigates long-term complications and improves visual outcome. The retrospective nature of this study limits substantial conclusions regarding any significant difference in outcome between AMT treatment methods. Nevertheless, the use of cryopreserved AMT rings has a similar outcome profile compared to use of dehydrated AMTs with symblepharon ring. Further research is needed to evaluate optimal AMT techniques.

ENDOGENOUS ENDOPHTHALMITIS ASSOCIATED WITH INJECTION DRUG USE COMPARED WITH OTHER ETIOLOGIES.

PURPOSE: To compare features of endogenous endophthalmitis associated with injection drug use (IDU) to endogenous endophthalmitis from other etiologies. METHODS: The authors retrospectively collected data on patients with endogenous endophthalmitis due to IDU or other causes from three academic tertiary care centers over a six-year period. Differences in presenting characteristics, culture results, treatment, and visual acuity were compared between groups. RESULTS: Thirty-eight patients (34%) had IDU-associated endogenous endophthalmitis while 75 patients (67%) had endogenous endophthalmitis from other causes. Compared with patients in the non-IDU group, IDU patients were significantly younger, more frequently male, had longer duration of symptoms at diagnosis, and were less likely to have bilateral disease ( P < 0.05 for all). Injection drug use patients were less likely to have a systemic infection source identified (29% vs. 71%, P < 0.001) or have positive cultures (47% vs. 80%, P < 0.001). The IDU group was less likely to be admitted to the hospital (71% vs. 92%, P = 0.005) and less likely to receive treatment with intravenous antimicrobials (55% vs. 83%, P = 0.003). Visual acuity did not significantly differ between groups. CONCLUSION: Endophthalmitis related to IDU presents in younger patients with less comorbidities and frequently without positive cultures or an identifiable systemic source; therefore, a high index of suspicion is needed to identify this disease.

High area deprivation index is associated with increased injury severity in pediatric burn patients.

BACKGROUND: Burn injuries play a significant role in pediatric injury-related mortality and morbidity. In this study, we aim to explore the relationship between patient demographics, socioeconomic factos and burn severity in pediatric patients. METHODS: Patients under age 14 hospitalized at Westchester Medical Center for burn injury between 2015 and 2021 were reviewed. Demographic variables including mechanism of burn, total body surface area (TBSA) involvement, surgical intervention, hospital length of stay (LOS), and LOS per TBSA burn were extracted. The Area Deprivation Index (ADI) was calculated to further assess socioeconomic factors. RESULTS: We included 399 patients under the age of 14 hospitalized for burn injuries at our institution between 2015 and 2021. The median age was 2 (IQR 1-6) years old, and 42.6% were female. High ADI (p = 0.018), Caucasian race (p = 0.001), and flame mechanism (p < 0.001) were independently associated with burn TBSA> 5%. LOS per TBSA was shorter in the Caucasian population (p = 0.022). CONCLUSION: In burn injury patients, further research is necessary to investigate modifiable risk factors in individuals of Caucasian race or lower socioeconomic status to target effective prevention campaigns.

Loss of Serpin E2 alters antimicrobial gene expression by microglia but not astrocytes.

Microglia are the brain-resident immune cells responsible for surveilling and protecting the central nervous system. These cells can express a wide array of immune genes, and that expression can become highly dynamic in response to changes in the environment, such as traumatic injury or neurological disease. Though microglial immune responses are well studied, we still do not know many mechanisms and regulators underlying all the varied microglial responses. Serpin E2 is a serine protease inhibitor that acts on a wide variety of serine proteases, with particularly potent affinity for the blood clotting enzyme thrombin. In the brain, Serpin E2 is highly expressed by many cell types, especially glia, and loss of Serpin E2 leads to behavioral changes as well as deficits in synaptic plasticity. To determine whether Serpin E2 is important for maintaining homeostasis in glia, we performed RNA sequencing of microglia and astrocytes from Serpin E2-deficient mice in a healthy state or under immune activation due to lipopolysaccharide (LPS) injection. We found that microglia in Serpin E2-deficient mice had higher expression of antimicrobial genes, while astrocytes did not display any robust changes in transcription. Furthermore, the lack of Serpin E2 did not affect transcriptional responses to LPS in either microglia or astrocytes. Overall, we find that Serpin E2 is a regulator of antimicrobial genes in microglia.

Barriers in Ophthalmology Residency Applications for Students Identifying as Underrepresented in Medicine: A San Francisco Match Analysis.

OBJECTIVE: There is a significant lack of ophthalmologists who self-identify as underrepresented in medicine (URiM) in the physician workforce. Prior literature has revealed bias in traditional metrics for selection relied on by resident programs such as United States Medical Licensing Examination (USMLE) scores, letters of recommendation (LOR), and induction into medical honors societies such as Alpha Omega Alpha (AOA). The purpose of this study was to elucidate race-based differences in word usage within ophthalmology residency letters of recommendation that may disproportionately affect URiM applicants. DESIGN: This was a retrospective, cohort study. SETTING: This was a multicenter study across the Wilmer Eye Institute at Johns Hopkins, the University of California San Francisco, and the University of North Carolina at Chapel Hill. PARTICIPANTS: San Francisco (SF) Match applications submitted to three ophthalmology residency programs between 2018 and 2020 were reviewed. URiM status, USMLE Step 1 score, and AOA membership were recorded. Letters of recommendation were analyzed using text analysis software. T-tests and chi-squared or Fisher's exact tests were used to compare continuous and categorical variables, respectively. Frequency of word/summary term usage in letters of recommendation were the main outcome measures. RESULTS: Relative to non-URiM applicants, URiM applicants had lower USMLE Step 1 scores (mean difference=7.0; p<0.001). Non-URiM letters of recommendation were more likely to describe applicants as "dependable" (p=0.009) and highlight "research" (p=0.046). URiM letters were more likely to describe applicants as "warm" (p=0.02) and "caring" (p=0.02). CONCLUSIONS: This study identified potential barriers for URiM ophthalmology residency applicants which can help guide future interventions to increase workforce diversity.

Molecular mechanism of hyperactivation conferred by a truncation of TRPA1.

A drastic TRPA1 mutant (R919*) identified in CRAMPT syndrome patients has not been mechanistically characterized. Here, we show that the R919* mutant confers hyperactivity when co-expressed with wild type (WT) TRPA1. Using functional and biochemical assays, we reveal that the R919* mutant co-assembles with WT TRPA1 subunits into heteromeric channels in heterologous cells that are functional at the plasma membrane. The R919* mutant hyperactivates channels by enhancing agonist sensitivity and calcium permeability, which could account for the observed neuronal hypersensitivity-hyperexcitability symptoms. We postulate that R919* TRPA1 subunits contribute to heteromeric channel sensitization by altering pore architecture and lowering energetic barriers to channel activation contributed by the missing regions. Our results expand the physiological impact of nonsense mutations, reveal a genetically tractable mechanism for selective channel sensitization, uncover insights into the process of TRPA1 gating, and provide an impetus for genetic analysis of patients with CRAMPT or other stochastic pain syndromes.

Surgical Management of Diabetic Macular Edema.

PURPOSE OF REVIEW: Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention. RECENT FINDINGS: Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.

Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination.

In the developing central nervous system, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes, which form myelin around axons. Oligodendrocytes and myelin are essential for the function of the central nervous system, as evidenced by the severe neurological symptoms that arise in demyelinating diseases such as multiple sclerosis and leukodystrophy. Although many cell-intrinsic mechanisms that regulate oligodendrocyte development and myelination have been reported, it remains unclear whether interactions among oligodendrocyte-lineage cells (OPCs and oligodendrocytes) affect oligodendrocyte development and myelination. Here, we show that blocking vesicle-associated membrane protein (VAMP) 1/2/3-dependent exocytosis from oligodendrocyte-lineage cells impairs oligodendrocyte development, myelination, and motor behavior in mice. Adding oligodendrocyte-lineage cell-secreted molecules to secretion-deficient OPC cultures partially restores the morphological maturation of oligodendrocytes. Moreover, we identified L-type prostaglandin D synthase as an oligodendrocyte-lineage cell-secreted protein that promotes oligodendrocyte development and myelination in vivo. These findings reveal a novel autocrine/paracrine loop model for the regulation of oligodendrocyte and myelin development.

Prdm16 and Vcam1 regulate the postnatal disappearance of embryonic radial glia and the ending of cortical neurogenesis.

Embryonic neural stem cells (NSCs, i.e., radial glia) in the ventricular-subventricular zone (V-SVZ) generate the majority of neurons and glia in the forebrain. Postnatally, embryonic radial glia disappear and a subpopulation of radial glia transition into adult NSCs. As this transition occurs, widespread neurogenesis in brain regions such as the cerebral cortex ends. The mechanisms that regulate the postnatal disappearance of radial glia and the ending of embryonic neurogenesis remain poorly understood. Here, we show that PR domain-containing 16 (Prdm16) promotes the disappearance of radial glia and the ending of neurogenesis in the cerebral cortex. Genetic deletion of Prdm16 from NSCs leads to the persistence of radial glia in the adult V-SVZ and prolonged postnatal cortical neurogenesis. Mechanistically, Prdm16 induces the postnatal reduction in Vascular Cell Adhesion Molecule 1 (Vcam1). The postnatal disappearance of radial glia and the ending of cortical neurogenesis occur normally in Prdm16-Vcam1 double conditional knockout mice. These observations reveal novel molecular regulators of the postnatal disappearance of radial glia and the ending of embryonic neurogenesis, filling a key knowledge gap in NSC biology.

Lymphocyte deficiency alters the transcriptomes of oligodendrocytes, but not astrocytes or microglia.

Though the brain was long characterized as an immune-privileged organ, findings in recent years have shown extensive communications between the brain and peripheral immune cells. We now know that alterations in the peripheral immune system can affect the behavioral outputs of the central nervous system, but we do not know which brain cells are affected by the presence of peripheral immune cells. Glial cells including microglia, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells (OPCs) are critical for the development and function of the central nervous system. In a wide range of neurological and psychiatric diseases, the glial cell state is influenced by infiltrating peripheral lymphocytes. However, it remains largely unclear whether the development of the molecular phenotypes of glial cells in the healthy brain is regulated by lymphocytes. To answer this question, we acutely purified each type of glial cell from immunodeficient Rag2-/- mice. Interestingly, we found that the transcriptomes of microglia, astrocytes, and OPCs developed normally in Rag2-/- mice without reliance on lymphocytes. In contrast, there are modest transcriptome differences between the oligodendrocytes from Rag2-/- and control mice. Furthermore, the subcellular localization of the RNA-binding protein Quaking, is altered in oligodendrocytes. These results demonstrate that the molecular attributes of glial cells develop largely without influence from lymphocytes and highlight potential interactions between lymphocytes and oligodendrocytes.

Global Dam Tracker: A database of more than 35,000 dams with location, catchment, and attribute information.

We present one of the most comprehensive geo-referenced global dam databases to date. The Global Dam Tracker (GDAT) contains 35,000 dams with cross-validated geo-coordinates, satellite-derived catchment areas, and detailed attribute information. Combining GDAT with fine-scaled satellite data spanning three decades, we demonstrate how GDAT improves upon existing databases to enable the inter-temporal analysis of the costs and benefits of dam construction on a global scale. Our findings show that over the past three decades, dams have contributed to a dramatic increase in global surface water coverage, especially in developing countries in Asia and South America. This is an important step toward a more systematic understanding of the worldwide impact of dams on local communities. By filling in the data gap, GDAT would help inform a more sustainable and equitable approach to energy access and economic development.

The effect of a brief, unplanned treatment delay on neovascular age-related macular degeneration patients: a retrospective cohort study.

Non-compliance to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy can result in increased disease activity in neovascular age-related macular degeneration (nAMD). Our study aims to determine effects of unplanned delay in anti-VEGF injection treatment for nAMD. This retrospective observational study included patients with delays in receiving intravitreal injections for nAMD treatment from March to May 2020 by at least 21 days. Baseline demographic and clinical characteristics, visual acuity (VA), central macular thickness (CMT) measured on optical coherence tomography (OCT), and duration of delayed treatment were analyzed for 3 time points, the pre-delay visit (v1) and post-delay visits (v2 and v3). Data were compared to age-matched controls treated for nAMD in 2019 without delay. Demographic characteristics were compared using two-sample t-tests for continuous variables and Pearson's chi-square tests for categorical variables. For the two primary outcomes of interest, VA and CMT, means and standard deviations were reported for each combination of group and time. Each outcome was modeled using a linear mixed model with the group, time and group-time interaction as fixed effects. A total of 69 patients (99 eyes) in the treatment delay group and 44 patients (69 eyes) in the control group were identified. Statistically significant differences between control and delayed groups were detected for VA (difference in mean logMAR = 0.16; 95% CI 0.06, 0.27; p = 0.002) and CMT (difference in mean CMT = 29; 95% CI 12, 47; p = 0.001) at v2. No differences were detected for v1 and v3 time points for both outcomes. An unplanned delay in intravitreal injection treatment for nAMD resulted in an increase in CMT and worsening of VA compared to controls observed at v2. At v3, CMT and VA recovered to near v1 levels. This study demonstrates that a one-time, brief interruption in treatment for nAMD results in reversible, temporary worsening.

Melanin-like Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration.

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.