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Treatment for Age-related Macular Degeneration

Image credit: https://irisvision.com/age-related-macular-degeneration/

Shubhankar Kulkarni
Shubhankar Kulkarni Jul 30, 2020
Question: Novel treatment approaches needed for Age-related Macular Degeneration.

Age-related Macular Degeneration (AMD) is the leading cause of irreversible vision loss among elderly people. Although the underlying cause of the development of AMD is not known, wet AMD is treated with antibodies against vascular endothelial growth factor (VEGF). (This leads us to another question discussed here). And currently, there is no treatment for dry AMD (although some are at the clinical stage).

When the lysosomal endonuclease Dnase2a (that degrades DNA fragments) was deleted, there was cytosolic accumulation of nuclear-DNA (nDNA) in RPE (retinal pigment epithelium) cells. The cells subsequently became senescent and secreted higher levels of VEGF and pro-inflammatory cytokines. These effects were mediated by the DNA sensor STING and mTOR pathway. Similar to other senescent cells, these senescent RPE cells secreted factors that acted in a paracrine manner and initiated senescence in neighboring healthy cells. These newly turned cells also started secreting VEGF as well as pro-inflammatory cytokines.

In light of these recent findings, in what way can we modify the existing treatment for AMD?

[1]Haijiang Lin, Bo Tian, Ahmad Al Moujahed, Joan W Miller, Demetrios G. Vavvas; Accumulation of damaged nDNA promotes RPE cellular senescence and pro-inflammation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5235.

Creative contributions

Can we find some treatment cues from the complement system?

Subash Chapagain
Subash Chapagain Nov 02, 2020
A crucial component of the innate immunity in mammals and higher animals, the complement system works for innate immunity to ward off possible lethal infections and inflammations. In humans, the complement system comprises a complex of at least 30 different enzymes and regulators, providing a robust immune defence mechanism. The complement molecules constitute around 5% of the total serum proteins, the liver being the main source of synthesis. Extrahepatic cells like monocytes, endothelial cells, epithelial cells, glial cells and neurons too produce complements . Both fluid phase and membrane-bound regulatory proteins are involved in complement regulation in order to prevent inadvertent damage as a consequence of complement activation.

A strong volume of evidence has been accumulated that the complement system may play a significant role in the pathogenesis of Age-related Macular Degeneration (AMD). Immune-mediated inflammatory events involving complement proteins have been implicated in the biogenesis of drusen, the small yellow deposits of fatty proteins (lipoproteins) that accumulate under the retina . Drusen deposition is one of the chief features of AMD as a clinical condition.

One of the important regulatory proteins in the complement system that is deemed to be related with AMD pathogenesis is the complement factor H (CFH) . A single polypeptide chain with a molecular weight of 155 kD, CFH is present in the plasma at a concentration of 110-645ug/ml. Constitutively produced in the liver, it is also synthesized by cells like lymphocytes, glomerular mesangial cells, neurons and glial cells. In the context of AMD, CFH synthesis occurs in the Retinoid Pigment Epithelial (RPE) cells and it accumulates in drusen.

Mutational screening of CFH genes in patients with AMD resulted in the identification of a polymorphism in the CFH gene. In different independent studies, the risk allele was identified as a tyrosine-histidine substitution at amino acid 402 of the CFH gene. Also, AMD patients with chromosome 1 mutations are reported to have complement overactivation in the extracellular matrix of the choriocapillaris, underlying Bruch’s membrane . Moreover, CFH deficiency has been found to cause type II membranoproliferative glomerulonephritis (MPGN II), a rare renal disease with coexisting drusen comparable to the molecular composition to those in AMD .

Though CFH is a major link between AMD and complement system, other components of the complement system like C3b, C5, MASP-2, CFB are also found to be involved in pathogenesis. Hence, one approach of treating AMD would be to target these targets in the complement system.

Drugs targeting specific complement components in AMD: Targeting C3b nad C3c

Compstatin is a 13-residue cyclic peptide that can selectively bind to C3b and C3c. AL-78898A, a Compstatin analog is one of the first complement inhibitors that was tested in macular degeneration, inciting a promise in the treatment studies . APL-2, a similar cyclic peptide, binds specifically to C3 and C3b and hence blocks all the three complement activation. In the Phase II trial, APL-2 showed a significant reduction in the rate of Geographic Atrophy (GA- a severe case of AMD). The reduction was 29% as compared to the control group after 12 months of monthly intravitreal injection . However, the treatment group had a higher risk of wet AMD. If corrected for this, APL-2 can serve as a suitable drug candidate for AMD.

Targeting Complement 5 (C5)

Eculizumab (also called Soliris) is the FDA-approved anti-C5 humanized monoclonal antibody (mAb) for the systemic treatment of paroxysmal nocturnal hemoglobinuria (PNH). It blocks C5a and C%b and thus shuts the downstream pathways that contribute to AMD. A complete study was done to assess its use in GA via intravenous infusion for safety and efficacy in AMD . It was found that the drug fully would not prevent GA, an advanced form of AMD. Inappropriate dosage and delivery of Eculizumab was attributed for the negative results. The comparatively larger size of the drug (148 kDa) might have made it difficult to penetrate to the major site of complement deposition of AMD .

Combining Eculizumab with another drug that controls upstream activation or another inhibitor can achieve better efficacy than the monotherapy . High attention should be paid to the risk of inhibiting general complement pathways.

Zimura (avacincaptad pegol, ARC1905) is a selective C5 inhibitor that was planned to be used in combination with anti-VEGF agents to provide synergistic effects to anti-VEGF monotherapy. Zimura, when used as supplementation with anti-VEGF therapy, has the potential to further enhance the efficacy in case of wet AMD, the phase-II trial that was completed in November 2018 has shown .

Targeting complement factor D (FD)

Lampalizumab (FCFD4514S)is the first therapeutic antibody that showed efficacy in clinical use in the selective blockade of alternative pathway (AP) (one of the three pathways in the complement system) by binding to the C-terminal portion of FD. Tests in cynomolgus monkeys suggested the potential of intravitreal injection of ant-complement FD as a treatment of AMD. 2 to 6 hours post-injection, serum AP activity was reduced . This drug can be potentially used if proven effective after clinical trials in humans.

Targetting MASP-2 protein

Mannose-binding protein-associated serine protease 2 (MASP-2) is a protein that functions in translating binding of the lectin complement pathway-recognition complexes into complement activation. As MASP-2 can autoactivate and generate a C3 convertase by its own, C3b generation and Lectin Pathway (LP) activation both can be prevented solely by blocking it. OMS721, a humanized IgG molecule has been developed against MASP-2. Though there have been no clinical trials for usage in AMD, researchers have indicated that anti-MASP-2 antibodies intraperitoneally reduce 50% of CNV in the laser-induced wet AMD afterwards .

Targeting Properdin
The only positive complement regulator that stabilizes C3 and C5 convertases and initiates the Alternative Pathway is properdin. Properdin was reported to be significantly present in 50% of the patients with wet AMD . mAb 1340 and NM9401 are two antibodies that bind properdin with high avidity and prevent its interaction with C3, resulting in AP cessation in vitro. This binding can be specific, and it has been speculated that therapeutic targeting of properdin may produce fewer side effects than inhibiting other components of the alternative pathway . As of now, both anti-properdin remain preclinical and yet to be tested in clinical studies.

Targeting complement factor B (CFB
Complement factor B (CFB) is a serine protease that is active in the early stages of the alternative complement cascade . Although there seems no significant increase of FB by itself in AMD, it can bind to properdin-bound C3b and further be cleaved by FD. IONIS-FB-LRx affects the AP by directly reducing the production of FB. It has undergone the Phase I trial with the sample size of 30 participants in 2017 to evaluate the safety and tolerability of two different doses (10 and 20 mg) administered subcutaneously .
MAb 1379 also inhibits AP at the level of factor B, keeping the rest complement system intact. Up to 4 μg of mAb 1379 is needed to fully inhibit AP in 10 μL of sera from various of species in vitro .

Apart from these individual monotherapies, combinatorial approaches might work. However, there is a need for full-proof efficacy and safety guarantee after phase-III clinical trials.

[1]Laufer J, Katz Y, Passwell JH . Extrahepatic synthesis of complement proteins in inflammation. Mol Immunol 2001

[2]Anderson DH, Mullins RF, Hageman GS, Johnson LV . A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002; 134 (3): 411–431.

[3]Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005; 308 (5720): 385–389.

[4]Mullins RF, Schoo DP, Sohn EH, Flamme-Wiese MJ, Workamelahu G, Johnston RM, et al. The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning. Am J Pathol. (2014) 184:3142–53. doi: 10.1016/j.ajpath.2014.07.017

[5]Mullins RF, Aptsiauri N, Hageman GS . Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye 2001; 15 (Part 3): 390–395.

[6]Leung E, Landa G. Update on current and future novel therapies for dry age-related macular degeneration. Expert Rev Clin Pharmacol. 2013;6(5):565–579. doi:10.1586/17512433.2013.829645


[8]Yehoshua Z, Filho CADAG, Nunes RP, et al. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology. 2014;121(3):693–701. doi:10.1016/j.ophtha.2013.09.044

[9]Mullins RF, Warwick AN, Sohn EH, Lotery AJ. From compliment to insult: genetics of the complement system in physiology and disease in the human retina. Hum Mol Genet. 2017;26(R1):R51–R57. doi:10.1093/hmg/ddx181

[10] Ricklin D, Mastellos DC, Reis ES, Lambris JD. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018;14(1):26–47. doi:10.1038/nrneph.2017.156

[11]ClinicalTrials.gov. ZIMURA in combination with LUCENTIS in patients with Neovascular Age Related Macular Degeneration (NVAMD). 2017. NLM identifier: NCT03362190.

[12]Loyet KM, Good J, Davancaze T, et al. Complement inhibition in cynomolgus monkeys by anti-factor D antigen-binding fragment for the treatment of an advanced form of dry age-related macular degeneration. J Pharmacol Exp Ther. 2014;351(3):527–537. doi:10.1124/jpet.114.215921

[13]Volz C, Pauly D. Antibody therapies and their challenges in the treatment of age-related macular degeneration. Eur J Pharm Biopharm. 2015;95:158–172. doi:10.1016/j.ejpb.2015.02.020

[14]Wolf-Schnurrbusch UE, Stuck AK, Hess R, Wolf S, Enzmann V. Complement Factor P in choroidal neovascular membranes of patients with age-related macular degeneration. Retina. 2009;29(7):966–973. doi:10.1097/IAE.0b013e3181a2f40f

[15]Lesher A, Nilsson B, Song W-C. Properdin in complement activation and tissue injury. Mol Immunol. 2013;56(3):191–198. doi:10.1016/j.molimm.2013.06.002

[16]Bansal R. Method of inhibiting complement activation with factor Bb specific antibodies WO2009/029669A1. 2009.

[17]Safety and efficacy of IONIS-FB-Lrx in up to 120 patients 55 and older with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). NLM identifier: NCT03446144 Available from: https://clinicaltrials.gov/ct2/show/NCT03446144?term=IONIS-FB-Lrx&rank=2.

[18]Thurman JM, Kraus DM, Girardi G, et al. A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice. Mol Immunol. 2005;42(1):87–97. doi:10.1016/j.molimm.2004.07.043

Promising new treatments for AMD

Darko Savic
Darko Savic Jul 30, 2020
Here is a list of some AMD treatments that are on the horizon https://www.aao.org/eye-health/tips-prevention/promising-new-treatments-amd

Using Senolytics to Treat AMD

Jamila Aug 03, 2020
As already mentioned, age-related macular degeneration (AMD) is characterized by a marked increase in senescent cells, and the senescence-associated secretory phenotype (SASP). (https://www.sciencedirect.com/science/article/abs/pii/S0306987712000291?via%3Dihub) Therefore, the usage of senolytics or senostatics to remove senescent cells or SASP respectively could be used as a novel treatment for AMD. Previous studies have shown that clearing senescent cells with senolytics can alleviate the symptoms of age-related diseases such as osteoarthritis, cardiovascular disease, renal disease, and much more.

(https://www.sciencedirect.com/science/article/abs/pii/S1931524420301468) Furthermore, the usage of senolytics such as the combination of dasatinib and quercetin has been associated with an improved lifespan in aged rats (https://pubmed.ncbi.nlm.nih.gov/29988130/) Quercetin is a naturally occurring flavonoid found in many fruits and vegetables. Quercetin has strong antioxidant properties but a low bioavailability, unfortunately. In a study, the solid dispersion of quercetin phospholipid complex (Q-SD) was prepared and used in a mouse model of dry AMD. It was found that Q-SD had an improved bioavailability compared to quercetin standalone. Furthermore, Q-SD had improved protective effects against retinal oxidative injury in the dry AMD model and these protective effects were related to enhanced Nrf2 signaling.

(https://www.hindawi.com/journals/omcl/2019/1479571/) Therefore, various senolytics should be further researched as a treatment for AMD.
Shubhankar Kulkarni
Shubhankar Kulkarni7 months ago
Unity Biotechnology will launch its Phase 1 study of UBX1325 (a novel senolytic) for patients with diabetic macular edema. UBX1325 targets the BCL-xL pathway and destroys senescent cells, like Navitoclax. However, UBX1325 has overcome the serious side effects of Navitoclax. Something similar to UBX1325 can be helpful. (Reference: https://www.lifespan.io/news/a-new-senolytic-enters-human-trials/)

Retinal Pigment Epithelium Replacement Therapy

Jamila Aug 04, 2020
Transplantation of healthy Retinal Pigment Epithelium (RPE) into patients with AMD may prevent further disease progression and may improve vision. The aim of RPE therapy is to replenish the RPE that is lost due to AMD and to protect the remaining photoreceptors from further damage. (https://www.annualreviews.org/doi/abs/10.1146/annurev-pharmtox-010919-023245) In a study by Sharma, an RPE injury was generated in pigs and then an iPSC-RPE patch was administered into a pig model. Sharma and colleagues found that the iPSC-RPE patch adjusted to the eyes prior to 10 weeks, the death of overlying photoreceptors was suppressed, and the phagocytosis of photoreceptor outer segments was enhanced. (https://stm.sciencemag.org/content/11/475/eaat5580.full) In June, the interim results for a clinical study conducted by Riemann were released. In the phase I/IIa clinical trial, healthy RPE was transplanted into human patients with dry AMD. It was found that RPE therapy was tolerated well by the patients and there were no adverse effects reported. Interestingly, there were changes in the appearance of the eyes, the characteristic drusen appearance seen in AMD patients was altered. (https://iovs.arvojournals.org/article.aspx?articleid=2766771) This research suggests that RPE transplants may have the potential to be a therapeutic option for AMD patients in the future.

Mitochondria Derived Peptides (MDPs) as potential treatment agents for AMD

Subash Chapagain
Subash Chapagain Jan 11, 2021
As compared to other cells, the Retinal Pigment Epithelium (RPE) cells have a higher metabolic activity due to which they lodge a large number of mitochondria, resulting in production and accumulation of the high amount of endogenous Reactive Oxygen Species (ROS). The mitochondria are prone to oxidative damage and the RPE seems to have a relatively lower rate of DNA repair .

RPE cells are postmitotic: hence the damaged mitochondria are not removed/recycled swiftly, leading to even more increased ROS generation that results in further mitochondrial damage. Apoptosis and low energy production-related with mitochondrial dysregulation is one of the initiating factors of AMD. In AMD, mitochondria are fragmented with an increased number of lesions. The ATP synthase activity is greatly altered and the nuclear-encoded protein transport is also compromised .

A class of peptides encoded by the Mt-DNA called the mitochondrial-derived peptides (MDPs) have emerged as potential agents that could be used to study and cure AMD. Especially, the MDPS encoded from the 16s rRNA region of the mtDNA namely Humanin and Small Humanin-like Peptides (SHLPs) are potentially the peptides that play key roles in cell survival and growth via distinct pathways. Some analogues of these peptides have been very-well characterized and are even in preclinical development for ageing-related diseases .

Out of all the MDPs, two, in particular, have been found so far to have implications in the case of AMD.


The first MDP discovered within the mammalian mitochondrial genome, Humanin is encoded from the 16S rRNA coding region of the mtDNA. It was first discovered from the occipital cortex of an Alzheimer’s disease patient brain . Humanin is a secretory 24-amino acid peptide with the amino acid sequence H-Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala-OH (H-MAPRGFSCLLLLTSEIDLPVKRRA -OH) and a molecular weight of 2687.26 Da. In non-polarized RPE cells, Humanin is expressed in the cytoplasmic compartments, chiefly localized in mitochondria . Humanin peptide was observed to render neuroprotection against a number of familial Alzheimer’s disease (FAD) genes like presenilin 1, presenilin 2 and mutated APP (Amyloid Precursor Protein) .

Humanin (HN) peptide exerst its effect by binding to the various receptors. Three such receptors have been reported so far: ciliary neurotrophic factor receptor (CNTFRα), the cytokine receptor (WSX1), and the transmembrane glycoprotein gp130- all of which are expressed in the RPE cells. When Humanin binds to heterotrimeric HN receptor (htHNR), the receptor subunits oligomerize, subsequently activating the classical JAK2 and STAT3 pathways . Additionally, more recent studies have shown that HN acts through GP130/IL6sT receptor complex, activating downstream AKT, ERK1/2 and STAT3 signalling pathways .

Another important observation is that the polarization of RPE cells increases Humanin levels by three-fold as compared to non-polarized cells. This suggests that the increase in HN is correlated with Oxidative stress (OS) -induced cell survival. Hinton et al have demonstrated in vitro, that HN rescues primary RPE cells from oxidative damage and prevents from subsequent cell death. These observations broadly show the Humanin’s effect of RPE cell protection occurs via two mechanisms: by enhancing mitochondrial biogenesis and function, and by activation of canonical STAT3. In RPE monolayers, Humanin mediated the suppression of OS-induced cell senescence and maintains transepithelial resistance, the study further showed . These factors establish Humanin peptide as a therapeutic candidate for the treatment of geographic atrophy in dry AMD.

Moreover, what is interesting about this peptide is that each of 24 amino acids in the Humanin have a specific function. Serine-14 has been linked with neuroprotection, but if it is replaced with glycine, the peptide generates a variant Humanin G (HNG) that is 1000 fold more potent than its parent analog. This provides opportunities to modify the parent peptide and see if the new variants have efficacy in preclinical studies .

Small Humanin-Like Peptides (SHLPs)

SHLPs are 24–38 amino acids long and each SHLP may differentially regulate mitochondrial and cellular health and functions. There are six different classes of SHLPs, but so far SHLP-2 has only been found to be implicated in regard to RPE cell functioning and AMD.
The level of SHLP2 in blood plasma has been known to decline with age, indicating that it has an important role in the ageing process. SHLP2 stabilizes the AMD mitochondria by preserving the mt-oxidative phosphorylation protein complex subunits (I-V) in AMD RPE trans-mitochondrial cells, and also promotes mitochondrial metabolism. Studies also have shown that exogenous application of SHLP2 peptide can enhance mitochondria-specific mtGFP fluorescence staining, increase the mtDNA copy numbers and furthermore upregulate the PGC-1α gene which is the master regulator of the mitochondrial biogenesis . Additionally, SHLP2 rescued and protected AMD RPE cybrid cells against amyloid-B-induced toxicity in vitro, further supporting its potential application in treatment, which might be used to delay the progression of AMD to its late form i.e., wet AMD.

All of this mentioned evidence and mechanisms are potential features of MDPs in AMD treatment, however, they are not conclusive. The effects of these MDPs on the angiogenesis-promoting factors need to be evaluated and examined if they are able to downregulate the pro-angiogenic factors and related pathways thereby seeing if they can suppress/prevent neovascularization in wet AMD. Long before these MDPs could be used for treatment, we will require the development of appropriate delivery techniques and formulations as well.

[1]J. Blasiak, S. Glowacki, A. Kauppinen, and K. Kaarniranta, “Mitochondrial and nuclear DNA damage and repair in age-related macular degeneration,” International Journal of Molecular Sciences, vol. 14, no. 2, pp. 2996–3010, 2013.

[2]F. Q. Liang and B. F. Godley, “Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration,” Experimental Eye Research, vol. 76, no. 4, pp. 397–403, 2003.

[3]Karunadharma, P.P.; Nordgaard, C.L.; Olsen, T.W.; Ferrington, D.A. Mitochondrial DNA. Damage as a potential mechanism for age-related macular degeneration. Invest Ophthalmol Vis. Sci. 2010, 51, 5470–5479.

[4]Fuku, N.; Pareja-Galeano, H.; Zempo, H.; Alis, R.; Arai, Y.; Lucia, A.; Hirose, N. The mitochondrial-derived peptide MOTS-c: A player in exceptional longevity? Aging Cell 2015, 14, 921–923.

[5]Hashimoto Y., Niikura T., Tajima H., Yasukawa T., Sudo H., Ito Y., Kita Y., Kawasumi M., Kouyama K., Doyu M., et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Abeta. Proc. Natl. Acad. Sci. USA. 2001;98:6336–6341. doi:10.1073/pnas.101133498

[6]P. G. Sreekumar, K. Ishikawa, C. Spee et al., “The mitochondrial-derived peptide humanin protects RPE cells from oxidative stress, senescence, and mitochondrial dysfunction,” Investigative Ophthalmology & Visual Science, 2016, vol. 57, no. 3, pp. 1238–1253, 2016.

[7]Y. Hashimoto, T. Niikura, Y. Ito et al., “Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer’s disease-relevant insults,” Journal of Neuroscience, vol. 21, no. 23, pp. 9235–9245, 2001.

[8]Y. Hashimoto, H. Suzuki, S. Aiso, T. Niikura, I. Nishimoto, and M. Matsuoka, “Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection,” Life Sciences, vol. 77, no. 24, pp. 3092–3104, 2005.

[9] S. J. Kim, N. Guerrero, G. Wassef et al., “The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling pathways and has age-dependent signaling differences in the hippocampus,” Oncotarget, vol. 7, no. 30, pp. 46899–46912, 2016.

[10]Yang L., Tan Z., Wang D., Xue L., Guan M.X., Huang T., Li R. Species identification through mitochondrial rRNA genetic analysis. Sci. Rep. 2014;4:4089. doi: 10.1038/srep04089.

[11]Nashine S., Cohen P., Nesburn A.B., Kuppermann B.D., Kenney M.C. Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration. Sci. Rep. 2018;8:15175. doi: 10.1038/s41598-018-33290-5.


Mohammad Shazaib
Mohammad Shazaib Sep 13, 2020
Age-related macular degeneration (ARMD) is the most common cause of irreversible central vision loss in the elderly populations of the industrialized world and will place increasing demands on health services as people live longer. For many years, the only treatment proven to be effective in arresting the progression of the wet form of ARMD was laser photocoagulation.[1] Even then, only a small proportion of patients within a specific disease subgroup have been shown to benefit from this treatment, and the rate of disease recurrence (paradoxically often under the fovea) is high. Lately, researchers have developed novel strategies based on improved understanding of the pathophysiology.[2] ANTIOXIDANT SUPPLEMENTATION For established dry ARMD, no treatment has been proven effective by randomized trials. However, subgroup analysis of a multicentre randomized placebo-controlled trial (AREDS trial) suggested that progression to advanced disease can be reduced in high-risk patients by daily supplements of vitamins C (500 mg) and E (400 IU), zinc (80 mg), and beta carotene (15 mg).[3] This approach was based on the hypothesis that free radicals are involved in pathogenesis and that oxidative damage to the retina might be prevented by antioxidant supplements.8,9 On the basis of these results the AREDS research group recommend that persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced ARMD; then, those with high-risk characteristics or with vision loss due to advanced ARMD in one eye, and without contraindications such as smoking, should consider taking supplements of antioxidants plus zinc.[4] Until lately, the outlook for patients with age-related macular degeneration was bleak; few were eligible for treatment with conventional laser photocoagulation. The novel treatments reviewed in this article, though not curative, offer at least the hope of visual stabilization.[5] Many of these treatments are now being assessed in large international multicentre trials. References 1. Klein R, Klein BEK, Linton KLP. Prevalence of age-related maculopathy, The Beaver Dam Eye Study. Ophthalmology 1992;99: 933-43 2. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related maculopathy in Australia. Ophthalmology 1995;102: 145060 3. Vingerling JR, Dielemans I, Hofman A, et al. The prevalence of age-related maculopathy in the Rotterdam study. Ophthalmology 1995; 102: 205-10 4. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: five-year results from randomized clinical trials. Arch Ophthalmol 1991;109: 1109-14 5. Macular Photocoagulation Study Group. Recurrent choroidal neovascularisation after argon laser photocoagulation for neovascular maculopathy. Arch Ophthalmol 1986;104: 503-12

P3HT nanoparticles

Martina Pesce
Martina Pesce Nov 04, 2020
In a study that was developed in my old lab when I was still working there they found a pretty cool solution.
They get the advantage of a particular property of this P3HT polymer: it transforms light into electricity. This is basically the same function of cones and rods, the cells that get damaged with macula degeneration.
The therapy would then consist of injecting in the convenient spot nanoparticles of this material. The dimension of it is very relevant to be sure to not damage the tissues around. Elegant, simple, brilliant.

This is on rodens but I know they are planning other species soon. Looking forward to the first humans trials!
Shubhankar Kulkarni
Shubhankar Kulkarni6 months ago
Martina Pesce That is really cool. Is that like a one-time therapy or does one need doses of the polymer for years? It is really helpful either way. It is also essential to check whether the natural chemicals in the eye (for example, proteases) damage the polymers.
Martina Pesce
Martina Pesce6 months ago
Shubhankar Kulkarni
Apparently, after 8 months the nanoparticles were still in the same place and still working. I guess we will have to wait to know if the effect stays longer than this.

I'm quoting their work when they say that these nanoparticles have "high biocompatibility due
to the intrinsic affinity of their chemical structure with that of biomolecules".
Which is actually pretty great since they do not damage the eye and don't get damaged themself.

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