New treatment could prevent dry age-related macular degeneration from transitioning to wet AMD, according to research. It targets leaky blood vessels by blocking key proteins. Current therapies also target leaky vessels in this regard.

Researchers found that the antidepressant fluoxetine can reduce inflammation and slow progression of dry AMD. Health insurance data demonstrated that those taking the drug had lower risks of developing vision-threatening diseases like AMD.

Antidepressant Fluoxetine

Age-related macular degeneration (AMD) is an eye disease that gradually leads to vision loss over several years, typically starting slowly over several months and manifesting itself with blurry central vision and distorted straight lines, difficulty reading, driving or recognising faces, as well as difficulty with reading, driving and recognising faces. Its symptoms often begin gradually and eventually turn severe. AMD affects depth perception and color vision. It’s thought to be caused by changes to the retinal pigment epithelium and macula – two structures responsible for retinal pigment epithelium changes – making it one of the leading causes of blindness among older adults. AMD can be divided into two distinct subcategories: dry and wet AMD. Dry AMD involves small deposits known as drusen developing in the retina which distort straight lines and blur central vision, while this form may progress into wet AMD which develops faster over time – leading to blindness among older adults.

Early stages of wet AMD involve abnormal blood vessels forming under the retina and leaking fluid, damaging its pigment epithelium and often leading to loss of vision. With early treatment such as injection of anti-vascular endothelial growth factor drugs into each eye (usually every month or every other month), anti-vascular endothelial growth factor therapy has been proven to significantly decrease growth of new blood vessels as well as slow the progression of wet AMD.

Fluoxetine, commonly marketed under its brand name Prozac, was shown to effectively treat wet macular degeneration with its ability to block an important protein called NLRP3. Researchers from University of Virginia found fluoxetine was chemically and functionally similar to CY-09 and could bind with NLRP3 similarly, blocking inflammation processes associated with wet AMD as well.

This team’s findings were published in PLOS One journal and involved comparing health claims data from over 100 million Americans collected between 2006 and 2018. After controlling for other known risk factors associated with AMD, researchers discovered that taking fluoxetine had an average 15 per cent lower risk of dry AMD. Furthermore, those taking it for extended periods had an even lower risk of the condition developing.

Stem Cell Therapy

Stem cell therapy offers promise as a treatment option for retinal diseases; however, its development remains at an early stage. Researchers are still trying to establish optimal stem cell types and delivery methods, testing how transplantation affects various stages of disease progression as well as hoping to increase best corrected visual acuity by replacing degenerating cells within the eye with newer, healthier ones.

Numerous studies have demonstrated the effectiveness of stem cell therapy in preventing and slowing vision loss, using autologous bone marrow, hiPSCs or retinal pigment epithelial cells to restore degenerated photoreceptor function. Results of trials vary and many lack randomised controlled trials; nonetheless, some have demonstrated that mesenchymal secretome has haemorheological, anti-inflammatory, neuroprotective properties which could promote retinal cell survival and function.

Implanting bioengineered patches of stem cells under the retina can also be an effective method for replacing degenerated cells, according to NYSCF-Robertson Stem Cell Prize recipient Peter Coffey and his team at University College London and University of California Santa Barbara. His approach utilizes non-diseased human RPE cells placed behind retinal rods and cones. Patients treated using this approach experienced significant improvements in vision; some went from not being able to read at all with glasses to reading 60-80 words per minute!

Researchers recently demonstrated that human iPSC-derived RPE cells could prevent photoreceptor loss in animal models of wet AMD. Based on this finding, they initiated a clinical trial where human iPSC-derived RPE will be transplanted directly into wet AMD patients’ subretinal space as the first use of human iPSCs to treat an inherited eye disease.

Manchester Royal Eye Hospital is one of only four UK sites selected to participate in a new investigational gene therapy trial for an advanced form of dry age-related macular degeneration known as geographic atrophy, which currently lacks effective treatments. GT005 seeks to inhibit expression of proteins linked to disease development – with completion set for 2023 under Gyroscope Therapeutics Limited’s trials.

Immunotherapy

Dry age-related macular degeneration involves a gradual breakdown of retinal pigment epithelium cells that lead to deposits known as drusen. Over time, these deposits build up and create distortions in straight-ahead vision as well as blurry areas called geographic atrophy in the center of visual field – one of the leading causes of blindness among older people robbing them of their ability to drive, read, and recognize faces.

Amsler grids can help identify any changes to central vision. After this, your eye doctor may use an instrument called a funduscopic examination to observe how your macular pigment epithelium is developing; depending on its results, ophthalmologists may also perform tests like angiogram or optical coherence tomography in order to ascertain if AMD has advanced into wet AMD or not.

if you suffer from wet or neovascular age-related macular degeneration, an ophthalmologist may use laser surgery to address abnormal blood vessels in your macula. This quick in-office procedure involves shining a laser light directly on those blood vessels which are growing or leaking and shrinks them down, stopping future expansion. Unfortunately, depending on where they lie in relation to your macula (fovea), treatment could result in permanent blurry vision in certain areas where laser light was targeted.

Columbia Retina Institute is testing GT005, an investigational gene therapy designed to stop wet AMD from progressing further, through a gene therapy trial. With approval from the FDA and receiving Fast Track status for its evaluation process, GT005 could stop its progression altogether – providing DNA encoded for complement factor I (a protein which prevents immune system attacks against retinal cells) via single injection subretinal.

Antidepressant medication used to manage depression also blocks inflammation that contributes to age-related macular degeneration, according to research conducted on health insurance data for those taking fluoxetine antidepressants such as Prozac or Citalopram (Lexapro). Researchers discovered this fact through health insurance data analysis which demonstrated a lower risk for later-life disease development for those who take these medications; their findings were presented during a webinar with Professor David Crabb and Ophthalmologist Christiana Dinah from City University London who are experts on this subject matter.

Gene Therapy

Researchers are developing gene therapy approaches designed to halt or slow the progress of dry AMD. This disease impacts the central retina (macula), leading to irreversible vision loss. There are two forms of macular degeneration: wet and dry. Neovascular conditions involve blood vessels leaking fluid into the eye while dry AMD involves no new vessels forming after those that have died have died (dry).

Studies involving genetic, biochemical and cell biology research have led to various therapies for dry AMD. Some therapies have proven successful in animal models; others are currently being evaluated in clinical trials. Examples include antioxidative medications, complement cascade inhibitors, neuroprotective compounds, visual cycle inhibitors and gene therapy as possible solutions.

The first gene therapy treatment tested on humans to address dry AMD is known as ophNdi1. This pioneering gene therapy treatment directly targets mitochondrial function in cells which have become dysfunctional due to dry AMD; mitochondria are responsible for providing energy to retinal cells; this ophNdi1 gene therapy seeks to improve their activity so as to prevent sight loss due to macular cell deaths caused by dry AMD patients.

GT005, another one-off gene therapy treatment currently under development by Gyroscope Therapeutics Limited, involves extracting cells from an individual and genetically altering them to express a protein which reduces inflammation. Initial trials have demonstrated its potential effectiveness in slowing the progression of dry AMD known as geographic atrophy.

Gene therapy research is also underway to create treatments for other hereditary retinal diseases such as Stargardt’s hereditary macular degeneration and X-linked RP. A key technique employed to do so involves injecting therapeutic genes using an Adeno-Associated Virus into an eye – an approach considered safe enough to use in numerous clinical trials.

Base and prime editing technology allows scientists to modify the genome of human retinal pigment epithelial cells using cutting techniques that insert foreign genetic sequences. It should be more effective than previous methods like RNA interference.