Lecture 9 (Macular Degeneration) Flashcards
What is macular degeneration?
Macular degeneration is an eye disorder that causes blindness. The condition affects the macula, which is the part of the retina responsible for central vision, and is linked to the death of retinal epithelial cells. Macular degeneration can be categorised into dry and wet, or AMD and genetic (e.g. Stargardt’s macular dystrophy).
How are retinal pigment epithelial cells damaged during macular degeneration, and how could a therapy be developed against this damage?
Retinal pigment epithelial cells in the retina help keep the photoreceptors healthy, however, in cases of macular degeneration they die off. If the retinal pigment epithelial cells can be replaced then macular degeneration can be halted, or even reversed; this approach has worked well in animal trials.
What is the prevalence of macular dystrophy, and who is most likely to be affected?
Nearly 8.5 million people are affected by macular degeneration in the U.S. alone (1.75 million are in the advanced stages)
Only about 10% have wet, 90% dry
Who will get it?
-Women
-People over age 65 have much higher risk
-Obese or inactive persons
-Smokers
-Light Pigmented Eyes
-People with a family history of the condition
Describe step 1 of the protocol for treatment of macular degeneration with human embryonic stem cells.
Step 1. Differentiate the hESC line into RPE cells and characterise them.
“The hESC master cell bank was thawed and expanded on mitomycin-C-treated mouse embryonic fibroblasts for three passages. After embryoid body formation and cellular outgrowth, we isolated pigmented RPE patches with collagenase. After purification and trypsinisation, the cells were expanded and cryopreserved at passage 2 for clinical use.
We characterised RPE in-process including karyotyping, pathogen and phagocytosis assay testing, and quantitative immunostaining for RPE and hESC markers.”
Describe step 2 of the protocol for treatment of macular degeneration with human embryonic stem cells.
Step 2. Surgical method to deliver the RPE cells into to retina.
“RPE was injected through a cannula delivering the targeted dose of 50,000 viable RPE cells into the subretinal space of each patient’s eye.”
Describe step 3 of the protocol for treatment of macular degeneration with human embryonic stem cells.
Step 3. Evaluate clinical – check cells remain in place in retina and are healthy
“After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months.”
Describe step 4 of the protocol for treatment of macular degeneration with human embryonic stem cells.
Step 4. Evaluate visual improvement
“Best-corrected visual acuity, monitored as part of the safety protocol, improved over half of the subjects in the study. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16-25 points 3-12 months after transplantation in patients with atrophic age-related macular degeneration and 8-20 points in patients with Stargardt’s macular dystrophy.”
Are there any side effects associated with the treatment of macular degeneration with human embryonic stem cells?
There are no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events are associated with vitreoretinal surgery and immunosuppression.
What are the religious beliefs regarding the use of embryonic stem cell technology?
Muslims: Maybe OK (fetus has moral existence only at the end of the 4th month)
Jews: Maybe OK (embryo has no moral status until 40 days)
Christians/Buddhists: NO (life begins at conception)
