Science topic

Macular Degeneration - Science topic

Macular Degeneration are degenerative changes in the retina usually of older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. It occurs in dry and wet forms.
Questions related to Macular Degeneration
  • asked a question related to Macular Degeneration
Question
4 answers
I'm doing a project to detect signs of Alzheimer's related macular degeneration, for which I would require a dataset of healthy and AD retinal images (ideally also in different stages of the disease), any suggestions of pre-existing datasets or how I might go about cobbling one together? Size and quality of the dataset aren't super high priority as it's a small POC.
Relevant answer
Hi did you find the dataset of retinal imaging for the detection of Alzheimer's?
Could you help me to find some database for this subject to?
Thank you in advance
  • asked a question related to Macular Degeneration
Question
3 answers
I know that different eye diseases (diabetic retinopathy, glaucoma, macular degeneration, and photophobia) can be diagnosed using retinal images, can we diagnose other human diseases related to different organs of the body from the fundus images?
Relevant answer
Answer
Roth spots (white centered retinal hemorrhage) can be seen in subacute bacterial endocarditis, leukemia and carbon monoxide poisoning.
  • asked a question related to Macular Degeneration
Question
3 answers
How to identify neurogenesis in adult human retina? Is there any good non-invasive method? This is an ethical, technical and tricky question which may give rise to important concepts. What techniques should be used to achieve this goal.
Relevant answer
Answer
It's a contentious question if consider it in human for which there is almost no evidence. In animal models there are certain reports, especially in Zebrafish. Just a lab have published a preprint about it. https://www.biorxiv.org/content/early/2016/06/08/057893
  • asked a question related to Macular Degeneration
Question
3 answers
optical coherence tomography (OCT) is used with considerable success to study retinal degeneration. I am trying to evaluate the status of biomarker discovery of neuro-retinal degeneration in Macular Degeneration using OCT and related imaging systems
Relevant answer
Answer
The potential of using OCT especially, swept source and OCTA for AMD may provide more markers that can predict macular degeneration.
This review covers the topic quite well. The potential of spectral domain optical coherence tomography imaging based retinal biomarkers. Int J Retina Vitreous. 2017; 3: 1.
Published online 2017 Jan 9. doi: 10.1186/s40942-016-0054-7
Additional sources:
1.de Sisternes L, Simon N, Tibshirani R, Leng T, Rubin DL. Quantitative SD-OCT imaging biomarkers as indicators of age-related macular degeneration progression predicting AMD progression using SD-OCT features. Invest Ophthalmol Vis Sci. 2014;55:7093–7103. doi: 10.1167/iovs.14-14918. [PubMed] [Cross Ref]
2. Wu Z, Luu CD, Ayton LN, Goh JK, Lucci LM, Hubbard WC, Hageman JL, Hageman GS, Guymer RH. Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration. Ophthalmology. 2014;121:2415–2422. doi: 10.1016/j.ophtha.2014.06.034. [PubMed] [Cross Ref]
3. Ouyang Y, Heussen FM, Hariri A, Keane PA, Sadda SR. Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration. Ophthalmology. 2013;120:2656–2665. doi: 10.1016/j.ophtha.2013.05.029. [PMC free article] [PubMed] [Cross Ref]
4.Choroidal Changes Associated With Subretinal Drusenoid Deposits in Age-related Macular Degeneration Using Swept-source Optical Coherence Tomography.
Laíns I, et al. Am J Ophthalmol. 2017.
5.Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT
November 2017Ophthalmology
DOI10.1016/j.ophtha.2017.09.028
I hope they can contribute to the solution of your question.
  • asked a question related to Macular Degeneration
Question
2 answers
Lysosomal Dysregulation is the major determinant of AMD pathobiology. There is tremendous prospect for nanoparticle delivery based drugs to restore lysosomal acidification in the retina. What is the status and prospects of these technologies?
Relevant answer
Answer
Unfortunately most of the research is focused on treating AMD especially the wet type with Anti VeGFs that have been extensively commercially funded. With more and more studies showing that ultimately these injections lead to loss of vision due to retinal atrophy and fibrosis, we need approches like you suggest to change treatment completely. It's high time we treat the root cause instead of just the clinical manifestations.
Though nanoparticles offer a novel alternative to conventional treatment, it is imperative that we use them responsibly.
  • asked a question related to Macular Degeneration
Question
3 answers
Role of intravitreal dexamethasone (Ozurdex) in combination with Ranibizumab for CNVM in age related macular degeneration?
Relevant answer
Answer
Tle latest findings An improved understanding of retinal neovascularisation is helping to explain the current limitations of anti-vascular endothelial growth factor (anti-VEGF) therapy and guiding the development of new therapeutic approaches, Patricia A D’Amore PhD told a symposium on neovascular age-related macular degeneration (AMD) during the 16th EURETINA Congress in Copenhagen, Denmark.
Dr D’Amore, Director of Research, Schepens Eye Research Institute of Massachusetts Eye and Ear, USA, gave delegates an updated look at the pathophysiology of the disease, incorporating new information regarding therapeutic targets and how they fit into current and future treatment strategies.
“The initiation of neovascularisation is thought to be caused by three separate events, all of which take place in and around the retinal pigment epithelium (RPE),” explained Dr D’Amore.
The first event is the disruption and dedifferentiation of the RPE. Drusen are the driving factor here, growing under the RPE and causing both injury to the RPE and subsequent dedifferentiation of the tissue, she said.
The next stage is an hypoxia-induced VEGF expression by RPE cells, and likely also by macrophages. In silico modelling has indicated that 63μm is the approximate drusen threshold size for oxygenation, said Dr D’Amore. “Drusen above this well-known size generate a region of RPE hypoxia, leading to the expression of VEGF. Also, the outer nuclear layer is thinner above high drusen, indicating that photoreceptor death is occurring.”
The third event is inflammation that occurs secondary to drusen accumulation. Whether inflammation is caused by the simple presence of drusen, or is something that develops later on is not yet known, she said. Regardless, inflammasomes, intracellular protein structures whose sole purpose is to activate pro-inflammatory cytokines, are detected in both geographic atrophy and neovascular AMD.
These factors drive a chronic pathologic process and are responsible for persistent VEGF production. Neovascularisation is the end-stage result.
So much for the initiation of neovascularisation but what about maintenance of these new vessels?
Bruch’s membrane is a physical and biochemical barrier to vessels from the choriocapillaris. A break in this membrane allows blood vessels to grow, and represents the transition to neovascular AMD.
“The reason that anti-VEGF treatment generally has a temporary effect is because the underlying disease process is not influenced by VEGF neutralisation. Despite anti-VEGF treatment, the RPE injury is not corrected, breaks remain in Bruch’s membrane, inflammation remains uninterrupted, the RPE remains hypoxic and VEGF production continues. Treating with anti-VEGF is like putting a band-aid on the problem,” explained Dr D’Amore.
It is suspected that if we can prevent the pericytes from contacting the endothelial cells, they will remain vulnerable to anti-VEGF treatment because they will not mature
NON-RESPONDERS
But why are there eyes that seem to be anti-VEGF non-responders? A subset of neovascular vessels are ‘mature’. Stable vessels have associated pericytes or smooth muscle cells and a complete basement membrane, which means that they have become differentiated vessels.
These mature, stable vessels are maintained via interaction between endothelial cells and pericytes. The endothelial cells generate platelet-derived growth factor (PDGF), which induces the migration of pericyte precursors. Pericyte coverage leads to inhibition of endothelial cell proliferation and production of basement membrane, which make neovascular vessels less vulnerable to anti-VEGF-induced disruption.
Dr D’Amore showed colourised optical coherence tomography-angiography images of large neovascular membranes at baseline and at weeks 4, 6 and 8 during anti-VEGF treatment.
“We can see from these images that, although much of the neovascularisation disappears from view, a large component of the vasculature remains, despite the presence of VEGF neutralisation,” she said.
“It is suspected that if we can prevent the pericytes from contacting the endothelial cells, they will remain vulnerable to anti-VEGF treatment because they will not mature,” said Dr D’Amore.
Pericytes also promote endothelial cell survival through chemical signalling and physical interactions, including production of VEGF by pericytes. Platelet-derived growth factor B (PDGF-B) is the target of a molecule called pegpleranib, developed by Ophthotech Corp. as Fovista®.
Patricia A D’Amore: 
patricia_damore@meei.harvard.edu
  • asked a question related to Macular Degeneration
Question
1 answer
Our goal is generate oxidative environment on the RPE cells with purpose of modeling dry AMD disease in vitro. How can we model an in vitro dry AMD model? What type of chemical do you suggest to be applied, in what concentration, what cycle? (Protocol)
Relevant answer
Answer
  • asked a question related to Macular Degeneration
Question
2 answers
Hi everybody,
Can anyone describe the exact protocol to set up this animal model of retinal degeneration?
My questions are as simple as:
    (i) When you put back to normoxia the mice at P12 (after the 5-days period of 75% hyperoxia), do you just take the cage outside the oxygen chamber back to the atmosphere normal room conditions or do you keep them in the cage and set up the oxygen rate to normoxia?".
   (ii) Could you provide me a list of the material I need to set up this model?
   (iii) Are there any trick I should know before starting?
   (iv) Are C57BL/6 sensitive to this treatment?
   (v) How do you manage the death of the feeder mother? I mean do you specially buy some feeder mice for each experiment or do you use some feeder mice from you animal facility?
Thanks a lot for all the answers to those questions and for all the détails you could bring into my knowledge!
Juliette
Relevant answer
Answer
I have found that it is potentially possible to use airtight cages for mice and perfuse them with oxygen under went in order to not fill the lab room with oxygen. I'm still looking for a cheap and good oxygen analyser for this work. 
  • asked a question related to Macular Degeneration
Question
1 answer
I need to know the levels of iron in normal human tears and in those from macular degeneration-related disorder, such as age-related macular degeneration (AMD). Is there any paper already published on this field? Thank you!    
Relevant answer
Answer
Following literature may help:
Vinetskaia MI, Iomdina EN. [Study of lacrimal fluid trace elements in several
eye diseases]. Vestn Oftalmol. 1994 Oct-Dec;110(4):24-6. Russian. PubMed PMID:
7871647.
Leitch EC, Willcox MD. Synergic antistaphylococcal properties of lactoferrin
and lysozyme. J Med Microbiol. 1998 Sep;47(9):837-42. PubMed PMID: 9736166.
Erdogan F, Eliaçık M, Senkal E, Erdur SK, Kulak K, Ipek IO. Evaluation of the
effects of serum iron levels on lacrimal gland secretion. Kaohsiung J Med Sci.
2015 Aug;31(8):426-31. doi: 10.1016/j.kjms.2015.06.003. Epub 2015 Jul 15. PubMed
PMID: 26228282.
  • asked a question related to Macular Degeneration
Question
7 answers
rs2244169 is associated with macular degeration.
Relevant answer
Answer
Harishankar,
Your first stop should be dbSNP at the NCBI. This is the organisation that assigns the 'rs' SNP identifiers
This page doesn't give an amino acid change for this particular SNP, so I would then check it's location in the UCSC genome viewer (the hg19/GrCh37.13 version of the genome is still the most useful to use, even though it's not the most recent). The location is chr11:57359802
This shows the SNP to be about halfway between the genes UBE2L6 and SERPING1, therefore it does not change any protein sequence. If this is truly linked to disease it must be via a regulatory function, or is possibly in linkage disequilibrium with a different functional variant.
  • asked a question related to Macular Degeneration
Question
13 answers
This SNP associated with macular degeneration.
Relevant answer
Answer
  • asked a question related to Macular Degeneration
Question
13 answers
What do you use for screening of retinal diseases except OCT and other expensive technologies? In developing country they are not available to cover all population. Moreover, if the territory of the country is huge.
Relevant answer
Answer
We are developing a Tele-OCT. Regional centers send OCT to main hospital. An innovative software analyzes  not-normal profiles and alerts retina specialist submitting the file in his smartphone.
  • asked a question related to Macular Degeneration
Question
3 answers
What is the risk of this causing a tumor? My focus is on RPE cells for macular degeneration.
Relevant answer
Answer
I do firmly believe that out of their own microenvironment all types of stem cells whether they are pluripotent or multipotent react in a very unrealistic manner. Basically, I would say that if I want to reconstruct a complete tissue in vitro to be transplanted in vivo, eventually I need to re-create a condition which is high similar to the "real" one. I would probably be named as "deviated", but if my goal is to repair a tissue in vivo, I prefer to work with a whole bunch of stem cells and other molecules, rather than just one type of stem cells which wont be enough to obtain what I would really need. The in vivo microenvironment is a very dynamic scenario and the contribution of each single type of stem cells will never be 100%, as reported from lab results. In fact, in each repair site this 100% is in reality something that takes place during different phases and performed by different actors present in small percentage...whether  they are MSCs, ESCs, HSCs or NSCs or GFs..... 
  • asked a question related to Macular Degeneration
Question
3 answers
My study is to do with stem cell therapy for macular degeneration.
Relevant answer
Answer
Generally speaking, someone requiring immunosuppression would be more susceptible to infections. Specifically, for the commonly used drug, Cyclosporine A, side effects can include; lowering of white blood cell count, nausea and loss of apetite, kidney malfunction leading to raised blood pressure and increased growth of bodily hair.
  • asked a question related to Macular Degeneration
Question
11 answers
My focus is on stem cells being used to treat macular degeneration. Can anyone please explain more about this topic to me? What exactly are the nutrients from animals and how are they used to cultivate the cells?
Relevant answer
Answer
The nutrients are essentially a mixture of organic and inorganic compounds including vitamins, minerals, trace elements and proteins. All of these chemicals/proteins have too many functions to name here but suffice to say they are needed for all aspects of a cells health and maintenance. Historically, proteins from animals were used in the form of serum to provide nutrition and mouse feeder cells were used to provide an extracellular matrix for cell attachment. These animal based products are still used in many labs for convenience and cost but are no longer necessary for routine maintenance of pluripotent stem cells (iPS and ES) cells. Xenofree substitutes for growth medium (e.g. Xenofree Essential 8 medium with human FGF2 and TGFBeta) and cell culture plate surface (synthemax, human vitronectin or laminin) are all suitable replacements that work well and ensure that future clinical grade stem cell products will be animal product free. Hope that helps.
  • asked a question related to Macular Degeneration
Question
13 answers
Should patients be able to choose whether they are given treatments that have risks, if they are told what the risks are? In relation to macular degeneration, the trials into stem cells as a cure won't be offered to patients for a very long time, even though it is very promising. Patients that are currently suffering from the condition will have irreversible damage to their eyes before stem cells are offered. 
Relevant answer
Answer
Good questions!   Overall, animal experimentation can only be justified when it provides essential information that can improve human health, which cannot be obtained in other ways - when suffering is minimised.  Given a choice, it's always preferable to work with non-animal methods because they are cheaper, quicker and more ethical.
Nevertheless, studies in animals are essential prior to moving new drugs into humans, since they flag up a lot of issues which are not human-specific or individual specific.  Early clinical trialsl are very safe overall because animal studies (plus other focussed studies, such as genetic toxicity testing) protect patients well.
Even so, animal studies are expensive, slow and ethically undesirable.  So they need to be preceded (and ultimately replaced) by non-animal studies which can filter out lots of bad compounds that are unfit for testing in animals.  As it happens, the non-animal methods used for this purpose are also turning out to be much better at detecting bad effects that can lead to infrequent and human specific adverse reactions than animal studies.  This is a hot area of science right now.
Animal studies are of limited use for assessing beneficial disease modifying effects of drugs.  This is especially true for inflammatory diseases and CNS diseases.   We don't really know why that is.  It's likely to be because animal models are unable to reproduce all of the complex processes that cause disease in humans.  Many people have tried and fail to tackle this problem using animals.  Hence my recommendation that we should now focus much more attention on non-animal methods. 
  • asked a question related to Macular Degeneration
Question
4 answers
I want to know the details about the public databases other than DR databases...
Relevant answer
Answer
Yes. Project Macula (http://projectmacula.cis.uab.edu) is a great online resource run by Christine Curcio in Ophthalmology at UAB. It has images and histology for AMD.
  • asked a question related to Macular Degeneration
Question
7 answers
The standard textbooks define wet AMD as a neovascular disease. The poor response of wet AMD towards macugen therapy (anti-VEGF against VEGF A 165, a selective antivascular form of VEGF) arises the question whether wet AMD is predominantely a neovascular disease or more than that an exsudative disease. What do you think?
Relevant answer
Answer
Wet AMD is both neovascular and exudative. Once these neo-vessels break through the Bruchs membrane and the RPE is interrupted , the barrier is affected and leak is there.
  • asked a question related to Macular Degeneration
Question
5 answers
They have different tertiary structures. What make it precisely the same? And which subject does this question belonged to? Hoping someone can add some proper topics!
Relevant answer
Answer
Dear Song Gong,
I can suggest this paper:
SERRANO, SOLANGE M.T. ; MAROUN, RACHID C. . Snake venom serine proteinases: sequence homology vs. substrate specificity, a paradox to be solved. Toxicon (Oxford), v. 45, p. 1115-1132, 2005.
Best regards
  • asked a question related to Macular Degeneration
Question
3 answers
Some keep activity at high temperature while some lose activity quickly at lower temperatures. How does tertiary structure control it?
My question came from an article cited below:
“Soy protein isolate was separated from the defatted soy flour, modified with various urea concentrations, and compression-molded into plastics. Differential scanning calorimetry showed that the temperatures of denaturation and the enthalpies of denaturation of the modified soy protein decreased as urea concentrations increased above 1 M. At the same urea concentration, molded plastics made from the modified soy proteins showed a similar temperature of denaturation as the modified soy protein, but a lower enthalpy of denaturation. ”——Thermal and Mechanical Properties of Plastics Molded from Urea-Modified Soy Protein Isolates
Relevant answer
Answer
To my knowledge the denaturing temperature is (at least partially) controlled by the number and coordination of intra-molecular electrostatic interaction (H-bonds, stacking effects). The tertiary structure determins which H-bonds will exist - and vice versa; it is not approbriate to distinguish cause and effect here.
  • asked a question related to Macular Degeneration
Question
5 answers
Do you have any experience with resistant CNV?
Relevant answer
Answer
See our paper: "Laser-resensitization of medically unresponsive neovascular AMD: Efficacy and Implications." at the ASRS, San Diego, August 12.
This includes tolerance to all anti-VEGF drugs..
  • asked a question related to Macular Degeneration
Question
4 answers
Do you ask for any image or blood exams? How often do you follow these patients?
Relevant answer
Answer
Joining in late; but I'd order glucose tolerance test. In our series (Retina 2012), we found a frequent association with diabetes. I don't do FFA to diagnose MacTel anymore, SD-OCT and Fundus Autofluorescence, if available, are good non-invasive alternatives. As Rajiv said, treatment is only indicated for SRNV (the membranes don't come from choroid, so CNV is probably less suited).
  • asked a question related to Macular Degeneration
Question
6 answers
I am looking for questionnaires, where individuals can give information on their visual capacities, such as near/far vision, color vision, stereopsis, visual field etc. and also diseases, such as Glaucoma, cataracts, AMD etc.
Are there any self-report instruments available?
Thanks,
Steffen
Relevant answer
Answer
Yes, there are series of self-reported questionnaires available. However, not all are good. I would like to direct you to my recent review paper, which lists out all the existing ophthalmic questionnaires and also provides a table with the recommended disease-specific questionnaires that have best measurement properties. The paper is "Khadka J et al . Quality assessment of ophthalmic questionnaires: review and recommendations. Optometry and vision science :2013;90:720-744. This paper was the featured in one of the feature issues of the Optom Vis Sci on "Measuring from Patients' perspectives." You can get the full text from my research gate page or from the journal website.
I appreciate other colleagues recommendations. However, both the NEI-VFQ and the VCM1 are not comprehensive and moreover are flawed psychometrically (i.e. measurement properties) in their original formats. I won't recommend to use them in their original forms. However, modified scales can be used. For the NEI VFQ, please read the papers by our group . Pesudovs K et al Remediating serious flaws in the National Eye Institute Visual Function Questionnaire. Journal of cataract and refractive surgery 2010;36:718-732. 2.
Unfortunately, there are no existing or good questionnaire to assess just color vision, visual field or stereopsis. However, several disease-specific questionnaires have specific items (questions) referring to these visual functions. My review paper may be useful in exploring them. For near vision/distance vision, the subscales of the NEI-VFQ or the near vision subscale of the NEI-RQL are good.
Please refer to this paper. McAlinden C, Khadka J et al. Psychometric properties of the NEI-RQL-42 questionnaire in keratoconus. Investigative ophthalmology & visual science 2012;53:7370-7374.
  • asked a question related to Macular Degeneration
Question
7 answers
The attached file is a proposal that shows how neural re-mapping maybe able to provide a simple non-invasive treatment for people suffering from the effects of glaucoma (tunnel vision) and other conditions that involve damage to the retina. It is stressed that this is not a cure - it is intended to provide the means by which more of the brain's processing power may be 're-engaged' and so improve the the visual experience of people suffering form retinal damage and macular degeneration.
Relevant answer
Answer
Nope, you're right. Tunnel vision can occur in glaucoma. Wonder why this is? Perhaps because of a thinner layer of ganglion cells in the periphery?