Figure 23.Diagram displaying theproduction andflow of aqueous
humour (AqH). (a) AqHproduced at the ciliary body in the eye flows
(green arrows) through two routes independently that control
AqH dynamics: (i) via the trabecular meshwork (TM) and Schlemm’s canal
(purple arrow) (conventional route) and (ii) via the
uveoscleral tract (orange arrow)(non-conventional route). (b)
The balance of (AqH) production at the ciliary body and elimination in
the anterior chamber establishes intraocular pressure (IOP) in the eye.
The yearlyrate of incidenceof uveitis (a sight-threatening inflammatory
disease of the eye)at the age between 20 and 60 years for both males and
females is estimatedto be with a frequency of 38–714 per 1,00,000
persons [137]. CORM-A1 is an example of CO-releasing compounds
tested for its effect on uveoretinitis and is the first example of water
soluble CO-releaser. Figure 24andScheme 4may be
referred for knowing the structural details and CO-releasing
process.Nicoletti et al. [138] showed that CORM-A1is helpful in
autoimmune responsive in uveoretinitis.
Figure 24. Chemical structure of CORM-A1
Scheme 4. Mechanism of CO release fromCORM-A1
Hydrogen Sulphide and ophthalmic Diseases
Being third latest member of gasotransmitters after NO and CO,
H2S has also been reported to exhibitnumerous roles in
maintaining normal physiological conditions [139].The generation of
H2S as discussed in its biosynthesis section mainly
involves the catalytic intervention of CBS, 3MST, CSE and CAT. The same
enzymatic actions have been found operational in all mammalian eyeballs
confined to several locations. Any irregularity in such a distribution
results in eye defects. So many investigations have been reported
detailing H2S donors as IOP regulating compounds,
retinal cell protection, antioxidative stress and ocular protein
modulation. Thus, H2S donors represent promising drugs
applicable in treating manifold ophthalmic diseases as discussed below:
Among different factors responsible for ocular defects as is known IOP
is the main reason for glaucoma neuropathy [140] and finally it is
stability between AqH of ciliary body and outflow AqH that matters
[141].By facilitating cyclic adenosine monophosphate (cAMP) the
outflow could be enhanced [142]. By allowing
H2S-donors like L-Cysteine and sodium hydrosulfide
(NaHS)to act on adenylyl cyclase and ATP-sensitivepotassium channels
(KATP) therefore could increase cAMP concentrations and
could make the outflow ofAqH easy [143].Similar investigation
conducted by Módiset al. reveals that H2S inhibits
phosphodiesterase (PDE) and enriches intramitochondrial cAMP levels and
results in the excitation of protein kinase A (PKA) to
infusebioenergetic consequences [144]. Similarly, another
compoundGYY4137 [Figure 25 ] has furnished positive results
in stabilizing IOP[145, 146].
Figure 30: Chemical structure of GYY4137
Concluding Remarks and Future Outlook
Gasotransmitters are, therefore, outstanding molecules having
significant biological signalling role. Considering the fact that the
scientific world is eager to design and develop molecular scaffolds in
this context to be declared as medical or clinical relevant, so many
questions are underway to be resolved. Half-life period, solubility,
chemical environment effects, pH, thermodynamics and kinetics, all are
among the queries being investigated in this field.The ocular diseases
and the factors responsible for such impairments do contain mechanistic
pathways half answered in relevance with gasotransmitters. Drug delivery
challenges, transportation, combinatory implications of drugs,
optoelectronic effects, etc. need to be explored in a more deepened way.
Moreover, could synthetic chemists bring forth a molecular system of
synergetic effect in a view to declare molecular designs having
potentiality of releasing more than one ‘gasotransmitter’molecules?