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Novel Therapeutic Targets for Glaucoma: Disease Modification Treatment, Neuroprotection, and Neuroregeneration

  • Jacky Man Kwong Kwong
  • Iok-Hou PangEmail author
Chapter

Abstract

Current treatments for primary open-angle glaucoma, be they medication or surgery, only manage the symptom of ocular hypertension. They do not address the underlying mechanisms of pathogenesis or pathophysiology of the disease. Therefore, they do not alter the progression of the glaucomatous pathological changes. In contrast, this chapter explores potential therapeutic targets that aim to correct and/or reverse the pathological changes based on our understanding of the molecular and cellular mechanisms involved in the disorder. Therapies based on these targets, which are related to the trabecular meshwork, retina, or optic nerve, if proven successful, will revolutionize the treatment of this devastating blinding disease.

Keywords

Glaucoma Therapy Therapeutic target Disease modification Neuroprotection Neurorescue Neuroregeneration 

Abbreviations

4-PBA

4-Phenylbutyrate

ACE

Angiotensin-converting enzyme

ACh

Acetylcholine

ADSC

Adipose tissue-derived mesenchymal stromal cell

AGIS

Advanced Glaucoma Intervention Study

APC

Adenomatosis polyposis coli

AT1-R

Angiotensin II type 1 receptor

Amyloid-β

BAMBI

BMP and activin membrane-bound inhibitor

BBB

Blood–brain barrier

BDNF

Brain-derived neurotrophic factor

BMP

Bone morphogenic protein

BMSC

Bone marrow-derived mesenchymal stromal cell

Brn

Brain-specific homeobox/POU domain protein

CIGT

Collaborative Initial Glaucoma Treatment Study Trial

CK1α

Casein kinase 1α

CNS

Central nervous system

CNTF

Ciliary neurotrophic factor

CNTG

Collaborative Normal Tension Glaucoma Study

DPSC

Dental pulp-derived mesenchymal-like cell

Dsh

Dishevelled

EAAT1

Excitotoxic amino acid transporter 1

ECM

Extracellular matrix

EGCG

Epigallocatechin-3-gallate

EMGT

Early Manifest Glaucoma Trial

EPO

Erythropoietin

ERG

Electroretinograph(y)

ERK

Extracellular signal-regulated kinase

ET

Endothelin

ETA

Endothelin A receptor

ETB

Endothelin B receptor

FasL

Fas ligand

Fz

Frizzled family receptors

GAP-43

Growth-associated protein-43

GGA

Geranylgeranylacetone/Teprenone

GLAST

Glutamate/aspartate transporters

GSK

Glycogen synthase kinase

HSF

Heat shock factor

HSP

Heat shock protein

IL

Interleukin

IOP

Intraocular pressure

JNK

c-Jun N-terminal kinase

LBP

L. barbarum polysaccharide

LRP

Lipoprotein receptor-related protein

MMP

Matrix metalloproteinase

MSC

Mesenchymal stromal cell

nAChR

Nicotinic acetylcholine receptor

NGF

Nerve growth factor

NMDA

N-methyl-d-aspartate

NMNAT1

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1

NO

Nitric oxide

NOS

Nitric oxide synthase

OEC

Olfactory ensheathing cell

ONH

Optic nerve head

OXPHOS

Oxidative phosphorylation

p75NTR

p75 neurotrophin receptor

PERG

Pattern electroretinograph(y)

POAG

Primary open-angle glaucoma

PP2A

Protein phosphatase 2A

PPS

Peripapillary sclera

RAS

Renin–angiotensin system

RGC

Retinal ganglion cell

ROCK

Rho-associated coiled-coil protein kinase

ROS

Reactive oxygen species

SAA

Serum amyloid A

sFRP-1

Secreted frizzled-related protein-1

TCF/LEF

T-cell factor/lymphoid enhancing factor

Tfam

Mitochondrial transcription factor A

TGF

Transforming growth factor

TM

Trabecular meshwork

TNF

Tumor necrosis factor

TPGS

d-α-Tocopherol polyethylene glycol 1000 succinate

TRK

Tropomyosin-related kinase

Txn

Thioredoxin

Txnip

Thioredoxin-interacting protein

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Stein Eye Institute, Glaucoma Division, Department of Ophthalmology, David Geffen School of Medicine, University of California Los AngelesLos AngelesUSA
  2. 2.Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science CenterFort WorthUSA

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