Lecture 8

Question 1

The ____ _____ space is the most immune privileged in the eye.

Answer 1

Sub Retinal

Question 2

Photoreceptors have HLA-___ but not HLA-___, so they are immune privileged, while RPE do have both, but are immune privileged because they produce inhibitory factors that suppress the _______ formation of certain lymphocytes.

Answer 2

HLA-1

HLA-2

Clonal

Question 3

Embryonic stem cells are ______, meaning they can give rise to ectoderm, mesoderm, and endoderm. They are relatively ____ to grow. They are likely to be rejected if ______ derived.

Answer 3

Pluripotent

Easy

Allogeneically

Question 4

Adult stem cells are ________, not giving rise to as many lineages as embryonic or iPSCs. Unfortunately, they are relatively _____ to harvest. Rejection is not likely if they are ______ derived.

Answer 4

Multipotent

Hard

Autologously

Question 5

iPSCs are ______, giving rise to all cell lineages (same as embryonic.) They are relatively _____ to grow, but keep in mind they will express a few genes of the cell type they were derived from. Rejection is ______ even if ______ derived (and likely if allogeneic) in that these cells may express self-protein that was not “seen” by the developing immune system, but it is not likely.

Answer 5

Pluripotent

Easy

Possible

Autologously

Question 6

One of the difficulties faced with replacement therapy is that retinal cells undergo _______ _______ after other cells die off so they may maintain continuous stimulation.

Answer 6

Synaptic Reoganization

Question 7

Use of HSCs for retinal regeneration works via fusing of the HSCs to ____ Glial cells. This induces the glial cells to reenter the cell cycle and differentiate into ______, thus replacing the damaged tissue. The HSCs can be enhanced with _____, which pre-activates the ______ signaling pathway which enhances fusion, decreases apop, favors proliferation and differentiation.

Answer 7

Muller Glial Cells

Photoreceptors

BIO

WNT signaling pathway

Question 8

rd10 mice have a _______ mutation, causing progressive retinal degen with photoreceptor death. Researchers found rescuing just some of the photoreceptors with fusion to HSCs and PCs also rescued non-fused photoreceptors.

Answer 8

Phosphodiesterase

Question 9

Rescue therapy can be achieved via RPE transplants that facilitate PR rescue via trophic factors such as BDNF, CNF, and BFGF, ANNNND they can also facilitate ________ via VEGF-A which is important because the ______ vasculature tends to die off with RPE death.

Answer 9

Angiogenesis

Choroid vasculature

Question 10

iPSC-derived ______ progenitor cells can be used for rescue. They migrate and help repopulate PRs. What’s good about their capacity to migrate, is they can be transplanted away from the _____ –> less risk of damage/detachment.

Answer 10

Neural Proegnitors (iNPCs)

Fovea

Question 11

Best disease provides a good example of when combinatorial (cell + gene) therapies are useful. The disease is caused by a mutation in ______, causing retinal degen. These mutated ______ are harvested, de-differentiated into _____, which undergo gene therapy to correct the mutation, and are then transplanted back into the patient where they differentiate back into _____.

Answer 11

RPEs

RPEs

iPSCs

RPEs

Question 12

RCS rats have a mutation in merTK, which causes issues with phagocytosing ______ segments of RP cells

Answer 12

Outer segments of RP segments.

Question 13

One particular experiment using iPSC-derived RPEs showed both rescue and ______. The RPEs rescued PRs in the _____ _____ layer, and even elaborated it, such that the _____ _____ layer didn’t just stop degenerating, but grew in “thickness” when compared to control. This suggested new growth of PRs.

Answer 13

Replacement

Outer Nuclear Layer

Outer Nuclear Layer