DIS - Glaucoma Histopathology I - Week 2 Flashcards
List 6 causes of optic neuropathy and note which is the primary genetic link. Also note which of the 6 neuritis falls under.
Inherited ON - primary genetic link Inflammatory/infectious ON - neuritis Demyelinating ON Toxic ON Compressive ON Ischaemic ON
Give two general appearances of optic neuropathy.
Swollen (oedema)
Pale (pallid)
List the two conditions associated with neuritis and note which of them apply to imflammatory/infectious ON and demyelinating ON.
Papillitis
Retrobulbar neuritis
Inflammatory/infectious ON - both
Demyelinating ON - retrobulbar neuritis
Distinguish what is meant by primary and secondary glaucoma.
Primary - other cause of the glaucoma
Secondary - due to other eye disease
Lis the two kinds of primary glaucoma.
Primary open angle glaucoma
Primary closed angle glaucoma
True or false
Primary closed angle glaucoma always has a high IOP
True
True or false
Primary open angle glaucoma always has a high IOP
False, it may or may not have high IOP
What is the normal rate of RGC loss due to ageing per year? What percentage of neurons are lost by age 80?
5,000 cells per eye per year due to apoptosis
Normally will lose ~30% by 80 years of age
What happens to the rate of RGC loss with glaucoma and by what process? What happens with an ischaemic trigger?
glaucomatous optic neuropathy gives accelerated loss of neurons by apoptosis
An ischaemic trigger results in sudden/complete loss
How long can you expect a normal NFL layer to last before all RGCs are dead naturally due to ageing?
~200 years
What is the mitochondria count like in the prelamina region and what does this signify?
Very dense in this region, signifying a high energy demand for axons here
Given the amount of mitochondria in the prelamina region, describe what mitochondrial abnormalities would promote (4).
Oxidative damage and inflammation
Energy depletion leading to axoplasmic stasis
Both promote apoptosis
What is the density of the capillary plexus in the lamina and about the optic nerve like? Descibe why and why it is this so important in neuropathy ().
Its very dense, so it can deliver oxygen and metabolites to axons/mitochondria to regionsof hgih energy demand
If compromised, it leads to hypoxia/ischaemia
What three pressure gradients are important in the health of the optic nerve and what can an imbalance between these two cause (2)?
Blood pressure and IOP vs post lamina tissue pressure
Imbalance can cause lamina bowing and/or scleral stretch
List 4 consequences of lamina bowing and scleral stretch, specifying which apply to each one.
Both can distort lamina pores to crink capillaries, reducing capillary perfusion to the lamina and peripapillary choroidal region
Collectively, what can a pressure gradient imbalance at the optic nerve head promote (3)?
Promotes neuroinflammatory processes as well as axonal and RGC apoptosis
What three structures at the optic nerve head are particularly susceptible to high IOP that contributes to neuropathy?
Axons
RGC soma
Microglia
Describe what happens when IOP increases, including what happens to the RGC (2) and glial cells and what it produces as a result.
Increased IOP activates RGC pressure receptors, which become stressed and have difficulty sustaining axoplasmic flows through the lamina cribrosa
Glial cells become reactive, increasing the production of TNFα
Consider the response of the glial cells to increased IOP. What does this activate and what does it result in?
TNFα activates inflammatory cascades which damage axons at the lamina
This stops retro-grade flows of neurotrophins
Explain how the glial response to increased IOP ultimately results in damage to the ONH, specifying where the damage occurs and how. Describe how this damage can result in optic disc cupping.
RGC soma and axons cannot survive without neurotrophins, and undergoes apoptosis
This leads to a thinning of the RNFL
The loss of axons weakens the lamina integrity, allowing it to bow backwards and the cup to deepen at the surface
Describe a consequence of optic disc cupping on local blood vessels.
It will crink local small vessels, compromising blood delivery to this and the peripapillary region
List and describe the two main mechanisms behind optic neuropathy in glaucoma.
Acute cell death subsequent to trauma/ischaemia, causing disruption of membranes and neuronal necrosis
Programmed cell death causing neuron apoptosis and autophagy