Albino Research Articles

Genetic Causes of Oculocutaneous Albinism in Pakistani Population.

Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to variants in one or two different known albinism-associated genes. All of the identified variants are predicted to be pathogenic, which was corroborated by several in silico algorithms and association with diverse clinical phenotypes. We report an individual affected with OCA carries heterozygous, likely pathogenic variants in TYR and OCA2, raising the question of a possible digenic inheritance. Altogether, our study highlights the significance of exome sequencing for the complete genetic diagnosis of inbred families and provides the ramifications of potential genetic interaction and digenic inheritance of variants in the TYR and OCA2 genes.

Hermansky-Pudlak Syndrome and Lung Transplantation: A Single Center Case Series

<h3>Introduction</h3> Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive disorder defined by oculocutaneous albinism, platelet storage disorder with resultant bleeding diathesis and pulmonary fibrosis leading to end-stage lung disease. Despite known bleeding diathesis, patients with HPS-related pulmonary fibrosis have successfully tolerated lung transplantation. We detail the lung transplant evaluation of 10 patients with HPS-fibrosis, as well as the outcomes of 6 patients transplanted at a single center in the United States. <h3>Case Report</h3> Between 2003 and 2019, 10 patients with HPS-related pulmonary fibrosis underwent lung transplantation evaluation at our center <b>(table 1 & 2).</b> Three patients were declined listing. Reasons included advanced multi-system disease, obesity, and severe protein malnutrition placing candidates at high risk for perioperative complications and morbidity. Seven patients were listed for lung transplant (<b>table 3</b>), with six undergoing transplantation. Three patients tolerated perioperative ECMO. The majority received intraoperative prophylaxis for their bleeding diathesis. Reported estimated blood loss was increased in those that did not receive intraoperative prophylaxis. One patient expired in the immediate post-operative period due to arterial ECMO cannula dislodgement. No allograft developed fibrosis. Two patients developed chronic rejection, but allograft lifespans were greater than 6 years. For surveillance biopsies, the majority received routine pre-treatment with desmopressin with no significant bleeding. One patient did not and sustained substantial pulmonary hemorrhage, requiring intubation. <h3>Summary</h3> Early lung transplant evaluation can be pursued in patients with HPS-pulmonary fibrosis. This case series illustrates that these patients tolerate extra-corporeal membrane oxygenation as a bridge to transplantation, and can safely undergo transplant surgery and surveillance transbronchial biopsies with the use of anti-hemorrhagic prophylaxis.

Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics.

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.

Genetic analysis of the barley variegation mutant, grandpa1.a

BackgroundProviding the photosynthesis factory for plants, chloroplasts are critical for crop biomass and economic yield. However, chloroplast development is a complicated process, coordinated by the cross-communication between the nucleus and plastids, and the underlying biogenesis mechanism has not been fully revealed. Variegation mutants have provided ideal models to identify genes or factors involved in chloroplast development. Well-developed chloroplasts are present in the green tissue areas, while the white areas contain undifferentiated plastids that are deficient in chlorophyll. Unlike albino plants, variegation mutants survive to maturity and enable investigation into the signaling pathways underlying chloroplast biogenesis. The allelic variegated mutants in barley, grandpa 1 (gpa1), have long been identified but have not been genetically characterized.ResultsWe characterized and genetically analyzed the grandpa1.a (gpa1.a) mutant. The chloroplast ultrastructure was evaluated using transmission electron microscopy (TEM), and it was confirmed that chloroplast biogenesis was disrupted in the white sections of gpa1.a. To determine the precise position of Gpa1, a high-resolution genetic map was constructed. Segregating individuals were genotyped with the barley 50 k iSelect SNP Array, and the linked SNPs were converted to PCR-based markers for genetic mapping. The Gpa1 gene was mapped to chromosome 2H within a gene cluster functionally related to photosynthesis or chloroplast differentiation. In the variegated gpa1.a mutant, we identified a large deletion in this gene cluster that eliminates a putative plastid terminal oxidase (PTOX).ConclusionsHere we characterized and genetically mapped the gpa1.a mutation causing a variegation phenotype in barley. The PTOX-encoding gene in the delimited region is a promising candidate for Gpa1. Therefore, the present study provides a foundation for the cloning of Gpa1, which will elevate our understanding of the molecular mechanisms underlying chloroplast biogenesis, particularly in monocot plants.

The presentation and outcomes of Hermansky-Pudlak syndrome in obstetrics and gynecological settings: A systematic review.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder with clinical manifestations of bleeding diathesis, multi-organ disease and variable oculocutaneous albinism (OCA). In women, it can cause life-threatening obstetric and gynecological (OB/GYN) bleeding. To summarize OB/GYN presentations, outcomes, and management strategies in women with HPS. Main databases (MEDLINE, EMBASE, Cochrane, PubMed, Web of Science Core Collection and Google Scholar) were searched from inception until June 30, 2020. Case reports/series of women with confirmed HPS. A systematic review using PRISMA guidelines. Methodological quality assessment performed using adapted Newcastle Ottawa scale. A total 29 pregnancies in 15 women and 2 gynecological patients were identified. Heavy menstrual bleeding (HMB), the most common bleeding symptom, was reported in 8/15 (53%) of women. HMB and post-partum hemorrhage (PPH) led to diagnosis of HPS in 5/17 (29%) women. Primary PPH was reported in 12/27 (44%) of viable pregnancies; half were major PPH. In 17 pregnancies with known HPS diagnosis, 9 had hemostatic cover with desmopressin and 8 with platelet transfusion. Major PPH occurred in 3/9 (33%) pregnancies covered with desmopressin compared with none in the platelet group. Diagnosis of HPS should be considered in women with OCA presenting with HMB or PPH. Hemostatic management options include desmopressin and platelet transfusion. Management should be multidisciplinary with close collaboration between OB/GYN and hematology teams.

Dopachrome tautomerase variants in patients with oculocutaneous albinism

Albinism is a clinically and genetically heterogeneous condition. Despite analysis of the 20 known genes, ~30% patients remain unsolved. We aimed to identify new genes involved in albinism. We sequenced a panel of genes with known or predicted involvement in melanogenesis in 230 unsolved albinism patients. We identified variants in the Dopachrome tautomerase (DCT) gene in two patients. One was compound heterozygous for a 14-bp deletion in exon 9 and c.118T>A p.(Cys40Ser). The second was homozygous for c.183C>G p.(Cys61Trp). Both patients had mild hair and skin hypopigmentation, and classical ocular features. CRISPR-Cas9 was used in C57BL/6J mice to create mutations identical to the missense variants carried by the patients, along with one loss-of-function indel. When bred to homozygosity the three mutations revealed hypopigmentation of the coat, milder for Cys40Ser compared with Cys61Trp or the frameshift mutation. Histological analysis identified significant hypopigmentation of the retinal pigmented epithelium (RPE) indicating that defective RPE melanogenesis could be associated with eye and vision defects. DCT loss of function in zebrafish embryos elicited hypopigmentation both in melanophoresand RPE cells. DCT is the gene for a new type of oculocutaneous albinism that we propose to name OCA8.

HERC2 and OCA2 genes polimorphisms in relation to the iris color variation of the Belarusian population

The human genetic phenotyping is one of the most intensely developing area of forensic genetics. Externally visible traits, including eye color, can be predicted by analyzing single nucleotide polymorphisms with a high predictive rate. We studied the polymorphisms rs12913832 and rs1800407 in the HERC2 and OCA2 genes, respectively, to evaluate its prognostic availability in relation to the iris pigmentation of the Belarusian population. For this, both eye images and DNA samples were collected from 314 individuals to analyze the key polymorphisms by the TaqMan assay. Our data confirmed a relevance of rs12913832:A&gt;G and rs1800407:G&gt;A in the prediction context. The highest values of the sensitivity (SE = 0.94) and the specificity (SP = 0.90) were obtained for rs12913832, demonstrating the high efficiency of this marker as a classifier of phenotypic groups. The presence of the ancestral dominant allele rs12913832-A causes a dark (brown) iris pigmentation, how- ever, the heterozygous state rs12913832:GA includes a range of mixed variants. The predictive value of rs1800407 for the genetic phenotyping is highly significant (SE = 0.98), but has a low specificity (SP = 0.14), thus rs1800407, not being an effective classifier, can be used as an auxiliary in the eye color predictive model. The analysis of a cumulative impact of the both poly- morphisms on the iris color variation shows their high prospects for the genetic phenotyping of the Belarusian population.

Perceptual learning improves visual functions in patients with albinistic bilateral amblyopia: A pilot study.

Several visual functions are impaired in patients with oculocutaneous albinism (OCA) associated to albinistic bilateral amblyopia (ABA). In this study, we aimed at exploring whether perceptual learning (PL) can improve visual functions in albinism. Six patients and six normal sighted controls, were trained in a contrast detection task with lateral masking. Participants were asked to choose which of the two intervals contained a foveally presented low-contrast Gabor patch. Targets were presented between higher contrast collinear flankers with equal spatial frequency. When increasing target-to-flanker distance, lateral interactions effect normally switches from inhibition to facilitation, up to no effect. Our findings showed that before PL, only controls showed facilitation. After PL, results suggest that facilitatory lateral interactions are found both in controls as well as in albino patients. These results suggest that PL could induce higher processing efficiency at early cortical level. Moreover, PL positive effect seems to transfer to higher-level visual functions, but results were not very consistent among tasks (visual acuity, contrast sensitivity function, hyperacuity and foveal crowding). Although a small sample size was tested, our findings suggest a rehabilitative potential of PL in improving visual functions in albinism.

Hermansky-Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease.

Pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a poor prognosis. Studying genetic diseases associated with pulmonary fibrosis provides insights into the pathogenesis of the disease. Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterised by abnormal biogenesis of lysosome-related organelles, manifests with oculocutaneous albinism and excessive bleeding of variable severity. Pulmonary fibrosis is highly prevalent in three out of 10 genetic types of HPS (HPS-1, HPS-2 and HPS-4). Thus, genotyping of individuals with HPS is clinically relevant. HPS-1 tends to affect Puerto Rican individuals due to a genetic founder effect. HPS pulmonary fibrosis shares some clinical features with idiopathic pulmonary fibrosis (IPF), including dyspnoea, cough, restrictive lung physiology and computed tomography (CT) findings of fibrosis. In contrast to IPF, HPS pulmonary fibrosis generally affects children (HPS-2) or middle-aged adults (HPS-1 or HPS-4) and may be associated with ground-glass opacification in CT scans. Histopathology of HPS pulmonary fibrosis, and not IPF, shows vacuolated hyperplastic type II cells with enlarged lamellar bodies and alveolar macrophages with lipofuscin-like deposits. Antifibrotic drugs approved as treatment for IPF are not approved for HPS pulmonary fibrosis. However, lung transplantation has been performed in patients with severe HPS pulmonary fibrosis. HPS pulmonary fibrosis serves as a model for studying fibrotic lung disease and fibrosis in general.

A mutant gene for albino body color is widespread in natural populations of tanuki (Japanese raccoon dog).

Albino mutants (white coat and red eyes) of tanuki (Nyctereutes procyonoides viverrinus) have been repeatedly found in the Central Alps area of Japan. We recently reported that an albino tanuki from Iida, a city in this area, lacks the third exon of the TYR gene encoding tyrosinase, which is essential for melanin synthesis. The absence of this exon was due to the chromosomal deletion of a complex structure. In the present study, we analyzed TYR of another albino tanuki that was found in Matsusaka, a city located outside the mountainous area. In this animal, the third exon was also lost, and the loss was due to a deletion in which the structure was identical to that of the Iida mutant. Our results indicate, in consideration of the complex structure of the deletion, that the two albino animals inherited a single deletion that arose in their common ancestor. Iida and Matsusaka are approximately 170 km apart. This is, to our knowledge, the first report of an albino mutant gene that is widely distributed in mammalian natural populations. As the origin of this mutation is not known, the distance covered by the mutant gene remains unclear. If we assume that the mutation occurred halfway between Iida and Matsusaka, we can predict the migration distance to be approximately 85 km; however, if the mutation occurred at any other place, a longer distance would be predicted. Natural selection against albino tanuki may be relaxed because of a recent increase in food resources and refuge in urban areas.

A rare case of Hermansky-Pudlak Syndrome with bruise and mellitus diabetes

Albinism is a hereditary disorder that causes decreased pigmentation (coloring) in the body. As a consequence, albinism individuals are mostly fair-skinned with light hair known as oculocutaneous albinism. Skin, hair and color of the eye may vary, however, as some people with albinism may have dark brown hair and green or hazel / blue eyes. In both cases, poor vision and varying degrees of nystagmus (uncontrolled side-to-side eye movements) are observed. Everyone with HPS has albinism but not all people with albinism have HPS. We recorded a case with multiple comorbidities of a 37-year-old female patient with Hermansky-Pudlak syndrome (HPS) here

Clinical utility gene card for oculocutaneous (OCA) and ocular albinism (OA)-an update.

Clinical utility gene card for oculocutaneous (OCA) and ocular albinism (OA)-an update.

Changes in plastid biogenesis leading to the formation of albino regenerants in barley microspore culture

BackgroundMicrospore embryogenesis is potentially the most effective method of obtaining doubled haploids (DH) which are utilized in breeding programs to accelerate production of new cultivars. However, the regeneration of albino plants significantly limits the exploitation of androgenesis for DH production in cereals. Despite many efforts, the precise mechanisms leading to development of albino regenerants have not yet been elucidated. The objective of this study was to reveal the genotype-dependent molecular differences in chloroplast differentiation that lead to the formation of green and albino regenerants in microspore culture of barley.ResultsWe performed a detailed analysis of plastid differentiation at successive stages of androgenesis in two barley cultivars, ‘Jersey’ and ‘Mercada’ that differed in their ability to produce green regenerants. We demonstrated the lack of transition from the NEP-dependent to PEP-dependent transcription in plastids of cv. ‘Mercada’ that produced mostly albino regenerants in microspore culture. The failed NEP-to-PEP transition was associated with the lack of activity of Sig2 gene encoding a sigma factor necessary for transcription of plastid rRNA genes. A very low level of 16S and 23S rRNA transcripts and impaired plastid translation machinery resulted in the inhibition of photomorphogenesis in regenerating embryos and albino regenerants. Furthermore, the plastids present in differentiating ‘Mercada’ embryos contained a low number of plastome copies whose replication was not always completed. Contrary to ‘Mercada’, cv. ‘Jersey’ that produced 90% green regenerants, showed the high activity of PEP polymerase, the highly increased expression of Sig2, plastid rRNAs and tRNAGlu, which indicated the NEP inhibition. The increased expression of GLKs genes encoding transcription factors required for induction of photomorphogenesis was also observed in ‘Jersey’ regenerants.ConclusionsProplastids present in microspore-derived embryos of albino-producing genotypes did not pass the early checkpoints of their development that are required for induction of further light-dependent differentiation of chloroplasts. The failed activation of plastid-encoded RNA polymerase during differentiation of embryos was associated with the genotype-dependent inability to regenerate green plants in barley microspore culture. The better understanding of molecular mechanisms underlying formation of albino regenerants may be helpful in overcoming the problem of albinism in cereal androgenesis.

Rapid action of Triiodothyronine on Mitochondrial H + , Ca 2+ and Mg 2+ -Dependent ion Transporters in Cortex, Hippocampus and Cerebellum of Restraint Mice

Thyroid hormones (TH) have a multitude of actions, mainly on development and differentiation during early life and play many vital roles in almost all tissues including neuronal tissues. TH rapidly alters the mitochondrial functions both by its genomic and direct actions on mitochondrial binding sites. The functional relationship between TH and mitochondrial ion transport during stress response has not yet been elucidated in mammals so far. Here, we report a rapid in vivo action of triiodothyronine (T 3 ) on mitochondrial ion transporter functions in the neuronal clusters of cortex, hippocampus and cerebellum of Swiss Albino mouse ( Mus musculus ) treated short-term with triiodothyronine (T 3 ; 200ng g-1) for 30 min either in non-stressed or in restraint-stressed (30 min each day for 7 days). The mH + -ATPase activity in the cortex decreased to significant levels after T 3 treatment in both non-stressed and restraint-stressed mice. On the contrary, the mH + -ATPase activity in the hippocampus and cerebellum increased to significant levels after T 3 treatment in both non-stressed and restraint-stressed mice. The mCa 2+ -ATPase activity in the cortex and cerebellum decreased to significant levels after T 3 treatment in both non-stressed and restraint-stressed mice. The mCa 2+ -ATPase activity in the hippocampus that increased to significant levels after T 3 treatment, showed a reversal after restraint-stress in T 3 -treated mice. The mitochondrial Mg 2+ -ATPase activity in the cortex decreased to significant levels after T 3 treatment in restraint-stressed mice. On the contrary, T 3 treatment in restraint stressed mice increased to significant levels the mitochondrial Mg 2+ -ATPase activity in the cerebellum. The mitochondrial Mg 2+ -ATPase activity in the hippocampus, which increased to significant levels after T 3 treatment in non-stressed mice, reversed its activity in T 3 -treated restraint-stressed mice. Spatial and differential action of T 3 on the mitochondrial ion transporters has been found in the present study that corroborates with a rapid modulatory action of T 3 on the transport of H + , Ca 2+ and Mg 2+ in the brain mitochondria of mice which appears to be sensitive to restraint stress.

Does Early Glasses Wear Improve Visual Outcome in OCA1A?

ABSTRACT Purpose: Oculocutaneous albinism type 1A (OCA1A), with lifelong absent melanin in skin, hair, and eyes, is the most severe type of albinism with greatest ametropia and poorest vision. We evaluated the relationship between age when spectacles were begun and visual outcome, in addition to status of refraction, in OCA1A. Methods: After IRB approval, a retrospective review of 70 consecutive charts of patients with OCA1A identified 24 fitting inclusion criterion of BCVA recorded at age 10–12 years. Exclusion criteria were those with other vision-threatening diagnoses and patients seen for a single visit. We recorded sex, age at beginning glasses, and refraction and BCVA at age 10–12 and most recent visit. Data were arbitrarily grouped by those initiating glasses at ≤ age 12 months and > age 12 months. Results: Regression analysis showed a larger degree of astigmatism was weakly associated with worse vision at age 10–12 years. A weakly positive relationship was found between poorer BCVA at last visit and older age at which glasses were initiated. All receiving glasses by age 1 and only half receiving glasses when older had improved visual acuity from age 10–12 years to last follow up. Conclusion: Additional study of a larger sample of this rare disorder is needed to determine if early glasses wear improves later BCVA.

Hermansky-Pudlak Syndrome and Genetic Diagnosis

Hermansky-Pudlak Syndrome (HPS) is genodermatosis, which is one of syndromic Oculo-Cutaneous Albinism (OCA). OCA categorizes 9 genes, and patients with mutations in HPS1 gene have greater likelihood of pulmonary fibrosis and granulomatous colitis for their 40s. In Juntendo university hospital, 39 patients had diagnosed as OCA during past 20 years. Only 5 patients were conducted gene analysis. 3 patients were OCA1B, and 2 patients were HPS1. In OCA patients, there are some gene mutations which onset serious complications. Early diagnosis by genetic test and early treatment is important.

Exploring the occupational engagement experiences of individuals with oculocutaneous albinism: an eThekwini District study

Background and aim : The World Federation of Occupational Therapists’ urges occupational therapists to recognise when people are being denied the right to participate in occupations and advocate for change. People with oculocutaneous albinism face stigma and discrimination owing to mythical beliefs surrounding the condition. This may negatively affect their engagement in occupations. Therefore, this study aimed to explore the occupational engagement experiences of individuals with oculocutaneous albinism within the eThekwini district. Method: A qualitative research design, using a phenomenological approach, was chosen to explore the participants lived experiences. Five participants were recruited using snowball sampling. Semi-structured interviews were used to obtain data which was analysed thematically. Results/ Findings : Data collected yielded three major themes: sense-of-self, barriers to occupational engagement and facilitators to occupational engagement. Four participants demonstrated a positive self-identity, which supported occupational engagement and aided the individual in overcoming barriers. Reasonable accommodations, social- and structural support facilitated occupational engagement, whilst myths and beliefs, physical limitations and the physical environment formed barriers to occupational engagement. Conclusio n: A new finding that emerged, indicated a change in self-perception, with participants adopting positive self-identities that facilitated occupational engagement. This may be attributed to participants belonging to the millennial generation, which is considered open-minded and deviating from tradition. Key words : Albinism, occupational engagement, barriers and facilitators to occupation. eThekwini District, KwaZulu-Natal, South Africa.

Prevalence of premalignant and malignant skin lesions in oculocutaneous albinism patients.

Oculocutaneous albinism describes a group of pigmentary disorders that lead to skin sensitivity and predisposition to skin malignances. To analyze clinical and epidemiological data in oculocutaneous albinism patients and to determine the prevalence of malignant skin lesions, assessing possible risk factors for skin cancer. Cross-sectional study evaluating epidemiological data, habits of sun exposure and sun protection, and clinical examination of albino patients followed in a reference dermatology outpatient clinic in Brasil. Our primary outcome was the occurrence of malignant skin lesions in biopsied tissues. Of 74 patients analyzed, 11 (15%) had one or more suspicious lesions and were biopsied, of which 8 (72.7%) patients presented with basal cell carcinomas, 7 (63.3%) presented with squamous cell carcinoma, and 1 (9%) presented with melanoma. Moreover, 32(43%) patients presented with actinic keratosis. Age, female gender, previous history of sunburn, history of malignant lesions and history of sun exposure without photoprotection were associated with the presence of malignant lesions. Unicentric, non-aleatory sample. There was a high prevalence of malignant and pre-malignant lesions in this population. Some potentially modifiable risk factors were associated with the occurrence of malignant skin lesions.

Single organelle measurements of melanosome pH using the novel ratiometric indicator RpHiMEL.

Melanocytes are specialized cells that produce melanin pigments responsible for skin, hair, and eye pigmentation. The synthesis and storage of melanin occurs in unique lysosome-related organelles called melanosomes, which regulate melanin production via complex regulatory mechanisms. Maintenance of the melanosome luminal ionic environment and pH is crucial for proper function of the main melanogenic enzymes. Defects in genes encoding pH-regulating melanosomal proteins result in oculocutaneous albinism, which is characterized by hypopigmentation, impaired vision, and increased susceptibility to skin and eye cancers. We recently uncovered several ion channels and transporters that modulate melanin synthesis by acidifying or neutralizing the luminal pH of melanosomes. However, our understanding of how melanosomes and other related organelles maintain their luminal pH is far from complete. The study of melanosome pH regulation requires robust imaging and quantification tools. Despite recent advances in the development of such methods, many limitations remain, particularly for quantitative analysis of individual organelle pH. In this chapter, we will provide an overview of the available methods used for melanosome pH determination, including their advantages, limitations, and challenges. To address the critical, unmet need for reliable melanosome pH quantification tools, we engineered a novel genetically encoded, ratiometric pH sensor for melanosomes that we named RpHiMEL. Here, we describe the design and optimization of RpHiMEL, and provide a pH quantification method for individual melanosomes in live cells. We demonstrate that RpHiMEL is a highly versatile tool with the potential to advance our understanding of pH regulation in melanosomes and related organelles.

Building Preclinical Models of Retinal Degeneration in Non-human Primates

Mutations affecting the expression of cone photoreceptors can lead to retinal degeneration, which in many cases can result in a permanent loss of vision. However, preclinical models for human retinal degenerative diseases are lacking. Dr Zi-Bing Jin and his colleagues study rhesus macaque models of achromatopsia (a congenital disorder characterised by an inability to distinguish colours) and oculocutaneous albinism (characterised by a disorder of melanin synthesis, leading to loss of visual acuity). The animal models utilised in the Jin laboratory offer important opportunities for studies on disease mechanisms as well as therapeutic development.