Lactoferrin and its nano-formulations in rare eye diseases

Singh, Jiya; Sharma, Mohita; Jain, Neha; Aftab, Insha; Vikram, Naval Kishore; Singh, T.P.; Sharma, Pradeep; Sharma, Sujata

doi:10.4103/ijo.ijo_303_22

Cited by 8 publications

(12 citation statements)

References 80 publications

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“…RP is a heterogeneous group of hereditary retinopathies with a large number of known mutations [ 11 ], several disease-causing genes, and extremely diverse clinical outcomes [ 7 , 9 ]. In the past two decades, remarkable progress has been achieved in locating the genes responsible for hereditary retinal conditions, including RP.…”

Section: Discussionmentioning

confidence: 99%

Molecular Genetic Analysis of the Autosomal Recessive Non-Syndromic Inherited Retinitis Pigmentosa

Habib¹,

Yasin²,

Namal³

et al. 2023

Cureus

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Introduction: 90% of visually impaired people live in developing countries. There are various types of vision impairment, but the focus of the current study is retinitis pigmentosa (RP). Up to now, 150 mutations have been reported that are linked with RP.Methodology: Healthy and affected members from two Pakistani families (RP01 and RP02) segregating autosomal recessive RP were selected for DNA extraction. PCR was conducted, and the amplified PCR products were analyzed using Polyacrylamide Gel Electrophoresis (PAGE) and visualized in the Gel Doc system for linkage analysis. The Gene Hunter 2.1r5 tool in the Simple Linkage v5.052 beta software suite was used to conduct multipoint parametric linkage analysis on the two consanguineous families examined on the 6K Illumina array. Exons and intron-exon borders of all known arRP genes found in homozygous areas were sequenced in the matching probands using a 3130 automated sequencer and the Big Dye Terminator Cycle Sequencing Kit v3.1. The mutation study was carried out using the AlaMut 1.5 program.Results: In both families, linkage analysis was performed using microsatellite marker DIS422 for gene crumbs homolog 1 (CRB1) and microsatellite marker D8S2332 for gene Retinitis Pigmentosa 1 (RP1). Multipoint linkage analysis identifies genomic regions that could potentially contain the genetic defect. In family RP01, only a single peak with a maximal multipoint LOD score of 3.00 was identified on chromosome 1, whereas in family RP02, multiple peaks with multipoint LOD scores of 1.80 were identified on chromosome 8. Analysis of the CRB1 gene revealed a homozygous substitution of glycine for valine (c.1152T>G; p.V243G), whereas the RP1 gene demonstrated that leucine was substituted for proline as a result of cytosine to thymine transfer (c.3419C>T; p. P1035L).Conclusion: Homozygosity mapping is a powerful method for finding genetic abnormalities that are both precise and comprehensive for identifying harmful variations in consanguineous families. This method is invaluable for providing accurate clinical diagnostic and genetic advice in remote regions of Pakistan while also increasing knowledge about autosomal recessive diseases and the dangers of mixing.

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Section: Discussionmentioning

confidence: 99%

Molecular Genetic Analysis of the Autosomal Recessive Non-Syndromic Inherited Retinitis Pigmentosa

Habib¹,

Yasin²,

Namal³

et al. 2023

Cureus

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“…Enter lactoferrin (LF), an iron-binding glycoprotein that originates from mucous cells and neutrophils. LF holds the unique capability to breach the BRB and exhibits substantial bioavailability ( 14 ). Notably, LF serves a dual function: it acts to chelate reactive iron within the retinal milieu, thereby curtailing the generation of ROS.…”

Section: Ferroptosis and Treatment Of Drmentioning

confidence: 99%

“…It stands as a pivotal constituent of the central nervous system, characterized by a bifurcated physiological and anatomical framework encompassing the neuro-retina and the retinal pigment epithelium ( 8 ) ( Figure 1 ). Concomitantly, the retina is endowed with elevated concentrations of polyunsaturated fatty acids, a salient attribute resonating profoundly within macular photoreceptors, rendering them remarkably predisposed to peroxidative challenges posed by reactive oxygen species (ROS) ( 14 , 15 ). Permeated by an inherent state of heightened metabolic activity, the retina registers as the most oxygen-consuming tissue per unit mass within the human anatomy ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the influence of light stands manifest, stimulating robust ROS production within photoreceptors, thus bequeathing a hyperoxic milieu ( 8 , 11 ). Ergo, the convergence of retinal structural attributes and the photo-oxidative milieu render it conspicuously susceptible to oxidative stress and inflammatory reactions elicited by ROS, thereby yielding photoreceptor degradation and ensuing visual impairments ( 14 ). Hence, safeguarding the microenvironment of the retina necessitates an imperative isolation from systemic circulation coupled with stringent defense mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…The oBRB coordinates the orchestration of nutrient-waste exchange, clearance of ROS, and oversight of inflammatory cell migration within the outer retinal domains, predominantly encompassing the choroid, Bruch’s membrane (BM), and retinal pigment epithelium (RPE) ( 8 ). Moreover, the melanin harbored by the RPE adeptly captures iron ions, effectively shielding the retina against oxidative damage ( 14 , 17 ). Conversely, the iBRB emerges as an amalgamation of the neurovascular unit (NVU), an architectonic ensemble instrumental in regulating the stability of the retinal microenvironment ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

Ouyang,

Zhou,

Wang

2023

Front. Endocrinol.

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Iron, as the most abundant metallic element within the human organism, is an indispensable ion for sustaining life and assumes a pivotal role in governing glucose and lipid metabolism, along with orchestrating inflammatory responses. The presence of diabetes mellitus (DM) can induce aberrant iron accumulation within the corporeal system. Consequentially, iron overload precipitates a sequence of important adversities, subsequently setting in motion a domino effect wherein ferroptosis emerges as the utmost pernicious outcome. Ferroptosis, an emerging variant of non-apoptotic regulated cell death, operates independently of caspases and GSDMD. It distinguishes itself from alternative forms of controlled cell death through distinctive morphological and biochemical attributes. Its principal hallmark resides in the pathological accrual of intracellular iron and the concomitant generation of iron-driven lipid peroxides. Diabetic retinopathy (DR), established as the predominant cause of adult blindness, wields profound influence over the well-being and psychosocial strain experienced by afflicted individuals. Presently, an abundance of research endeavors has ascertained the pervasive engagement of iron and ferroptosis in the microangiopathy inherent to DR. Evidently, judicious management of iron overload and ferroptosis in the early stages of DR bears the potential to considerably decelerate disease progression. Within this discourse, we undertake a comprehensive exploration of the regulatory mechanisms governing iron homeostasis and ferroptosis. Furthermore, we expound upon the subsequent detriments induced by their dysregulation. Concurrently, we elucidate the intricate interplay linking iron overload, ferroptosis, and DR. Delving deeper, we engage in a comprehensive deliberation regarding strategies to modulate their influence, thereby effecting prospective interventions in the trajectory of DR’s advancement or employing them as therapeutic modalities.

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Biomedical and Nutritional Applications of Lactoferrin

Coccolini,

Berselli,

Blanco-Llamero

et al. 2023

Int J Pept Res Ther

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Lactoferrin (Lf) is a glycoprotein belonging to the transferrin family, which can be found in mammalian milk. It was first isolated from bovine milk in the 1930s, and later in the 1960s, it was determined from human milk. This multifunctional protein has the specific ability to bind iron. It plays various biological roles, such as antibacterial, antiviral, antifungal, anti-tumour, anti-obesity, antioxidant, anti-inflammatory and immunomodulatory activities. There are several studies describing its use against in various cancer cell lines (e.g., liver, lung and breast) and the glycoprotein has even been reported to inhibit the development of experimental metastases in mice. Previous studies also suggest Lf-mediated neuroprotection against age-related neurodegenerative diseases and it is also expected to attenuate aging. More recently, Lf has been proposed as a potential approach in COVID-19 prophylaxis. In this review, we discuss the recent developments about the biological activities of this pleiotropic glycoprotein that will reason the exploitation of its biomedical and supplementary nutritional value.

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Lactoferrin and its nano-formulations in rare eye diseases

Cited by 8 publications

References 80 publications

Molecular Genetic Analysis of the Autosomal Recessive Non-Syndromic Inherited Retinitis Pigmentosa

Molecular Genetic Analysis of the Autosomal Recessive Non-Syndromic Inherited Retinitis Pigmentosa

Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

Biomedical and Nutritional Applications of Lactoferrin

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