Protein Changes May Stop Macular Degeneration

Identifying causes of disease through the intricacies of immunology and biochemistry has been short of groundbreaking. When it comes to macular degeneration, some scientists are attacking it by removing discovered degenerating factors revolving around specific biomarkers, namely deep seated proteins.

It turns out that protein changes may stop macular degeneration. Preliminary studies show some future promise of how manipulating proteins presents the ability to shut down AMD before it becomes a blinding problem. It is a painstaking process but in the end may be one of many applications capable of breaking the ruthless cycle of such a debilitating disease.

Wayward Waste 

They are called lipofuscin bis-retinoids (lie-po-few-sin bi-ret-in-oydz). Although not technically considered a protein, these molecules make up waste that accumulates on the proteins of the RPE (retinal pigment epithelial ). The RPE works with photoreceptor function, essential for healthy sight, but when blocked with these waste particles macular degeneration can occur.

In the study, ‘Structures and biogenetic analysis of lipofuscin bis-retinoids’ published by the National Center for Biotechnology Information, it was stated,

“Time-dependent lipofuscin accumulation in retinal pigment epithelial (RPE) cells has been notoriously deemed as a major risk factor in association with age-related macular degeneration (AMD)…With regard to treatment for AMD, some attempts at mediating the retinoid cycling rate have been made by utilizing the exogenous small-molecule inhibitors of 11cRDH, RPE65, retinol binding protein and transthyretin. Indeed, these compounds slow lipofuscin accumulation in RPE cells of the eye. Thus, it will be a promising strategy to screen a large body of low-molecular-weight antagonists limiting the visual cycle with an eventual aim of developing clinical medicines in favor of alleviating AMD.”

In advanced stages of genetic RPE degeneration, this waste accumulates more rapidly causing blindness as early as age 30. Researchers are now studying the effects of removing this waste from the RPE proteins. There is also consideration of stopping these proteins from allowing lipofuscin bis-retinoids to attach to them. This is in regard to the mention above of “exogenous small-molecule inhibitors of 11cRDH, RPE65, retinol binding protein and transthyretin”.

Stop Them, Wake Them Up

Another research project involves stopping specific proteins found on the macular and waking them up. When a healthy retina functions, the photoreceptor rods and cones send signals to other nerves called post-photoreceptor cells. It is believed that when macular degeneration deteriorates the rods and cones, it is the proteins on the post-photoreceptor cells that, with some medical intervention, may be able to takeover the job and enable sight to be restored.

According to research at the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago,

“Functional post-photoreceptor cells suggest an opportunity to restore sight in AMD patients. Our idea is to develop molecular structures (tiny machines) that would interact with specific proteins on the surfaces of these cells and stimulate them in response to light that enters the eye.”

Overall, this research is yet another ‘workaround’ attempt developed in the lab which utilizes hidden anatomical capabilities, either discoverable by humans or placed there by nature in the first place.

Dying Proteins Replaced

When one develops AMD, it is the RPE cell proteins that are terminated first. After this occurs, the photoreceptor cell proteins cannot survive which eventually leads to blindness. Researchers have attempted to replace dead RPE cells with live ones but have had minor success. Enter researchers from the University of Toronto Engineering.

Professor Molly Shoichet and her team decided to combine, in one injection, the replacement of not one but both dying cells. Specially prepared in what is called a hydrogel, healthy RPE cell proteins and healthy photoreceptor cell proteins are intricately injected into the eye.

Medical Xpress reports on this description,

“The hydrogels ensure an even distribution of cells, reduce inflammation and promote tissue healing in the critical early days post-injection. Eventually, they degrade naturally, leaving the healthy cells behind….The team tested co-injection in a degenerative mouse model resembling AMD. In a paper recently published in the journal Biomaterials, they report that mice who received the co-injection regained about 10 percent of their normal visual acuity. Those who received either cell type on its own showed little to no improvement.”

Ten percent may not sound like much but it can be a highly significant enhancement for someone struggling with AMD. It is also a preliminary number and as the research continues it is highly likely that perfecting the combination injection of RPE and photoreceptor cells will considerably repair compromised vision.

TLR2 Activation and Immune Response

An autoimmune disease is essentially a disease in which the body’s immune system inexplicably attacks healthy cells. Researchers are baffled by this response and have only found ways to stop the attack rather than discover and disable what causes it. TLR2 activation is the immune response to a microbial infection in the eye. This activation is a result of a protein called carboxyethylpyrrole (CEP). However, CEP is highly prevalent in people diagnosed with AMD, a non-microbial disease. 

In a research study titled, ‘Investigating if an Uncontrolled Immune Response to Your Own Damaged Cells Causes the Progression of AMD’ by Sarah L Doyle, BA, PhD Trinity College Dublin (Dublin, Ireland) the AMD immune response is described,

“Typically, inflammatory responses of the immune system are caused as a result of microbial infection. However, in chronic conditions, a form of “sterile” inflammation can exist in areas of the body in response to damaged “self-elements” in the absence of infection, due to uncontrolled activation of immune system sensors.”

Doyle and her research team believe that by following the instigation of CEP protein production without a microbial antagonist and targeting TLR2 activation with pharmaceutical therapeutics could lead to stopping this autoimmune response. By interrupting this process, there is a chance that excessive blood vessel growth (a leading cause of AMD) can be stopped.

These research projects are highly detailed and complex but this is what it takes to cure a disease as elusive as AMD. Digging deep into the biological process and either developing a workaround or getting to the root of the cause is essential. Targeting protein changes may stop macular degeneration in a diverse, unexpected way and researchers are getting closer to it every day.  

Sources:

https://www.brightfocus.org/macular/grant/investigating-role-toll-receptor-2-signaling-pathogenesis-amd

https://www.brightfocus.org/macular/grant/removal-lipofuscin-bisretinoids-rpe-v-cyclodextrins

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773547/

https://www.brightfocus.org/macular/grant/nanoscale-modulators-retinal-postsynaptic-receptors

https://www.google.com/amp/s/medicalxpress.com/news/2020-08-cell-technique-reverse-vision-loss.amp