Diabetic pupillary defect

Medical lesion in diabetes usually spare the pupil, comparing with

surgical lesion(aneurysm ...) which involve the pupil.

This is because of the microangiopathy which involves the vasa nervorum

.., causing ischemia of the

main trunk of nerve, and sparing the superficial pupillary fibers ..

While spare the pial vessels which supply the superficial Pupillomotor
parasympathetic fibers

Several different factors have been implicated in this pathogenic pro- cess.
Hyperglycemic activation of the polyol pathway leading to accumulation of
sorbitol and potential changes in the NAD:NADH ratio may cause direct neu-
ronal damage and/or decreased nerve blood flow (9 –11)

Diabetic Autonomic
Neuropathy

AARON I. VINIK, MD, PHD1 BRAXTON D. MITCHELL, PHD3 RAELENE E. MASER, PHD2
ROY FREEMAN, MD4
PATHOGENESIS OF DAN

Hypotheses concerning the multiple etiologies of diabetic neuropathy include a

metabolic insult to nerve fibers, neurovas- cular insufficiency, autoimmune
damage, and neurohormonal growth factor defi- ciency (8). Several different
factors have been implicated in this pathogenic process. Hyperglycemic activation
of the polyol pathway leading to accumulation of sorbitol and potential changes in
the NAD:NADH ratio may cause direct neu- ronal damage and/or decreased nerve
blood flow (9 –11). Activation of protein kinase C induces vasoconstriction and
re- duces neuronal blood flow (11). Increased oxidative stress, with increased free
radical production, causes vascular endothelium damage and reduces nitric oxide
bioavailability (12,13). Alternately, excess nitric oxide production may result in
formation of peroxynitrite and damage endothelium and neurons, a process re-
ferred to as nitrosative stress (14,15). In a subpopulation of individuals with
neuropathy, immune mechanisms may also be involved (16 –18). Reduction in
neurotrophic growth factors (19), deficiency of essential fatty acids (20), and
formation of advanced glycosylation end products (localized in endoneurial blood
vessels) (21) also result in reduced endoneurial blood flow and nerve hypoxia with
al- tered nerve function (8,11,12). The result of this multifactorial process may be
activation of polyADP ribosylation depletion of ATP, resulting in cell necrosis and
activation of genes involved in neuronal damage (22,23).
▪ Sympathetic innervation for ocular structures originates in segments T-1
through T-3.
▪ Ocular structures supplied by the sympathetic system are the iris dilator,
ciliary muscle, smooth muscle of the lids, lacrimal gland, and choroidal and
conjunctival blood vessels.
 In the sympathetic pathway the neurotransmitter released by the
preganglionic fiber is acetylcholine, and the neurotransmitter released by
the postganglionic fiber is norepinephrine.
 In the parasympathetic system both preganglionic and postganglionic fibers
secrete acetylcholine.
 Fibers that release acetylcholine are called cholinergic, and fibers that
release norepinephrine are called adrenergic.
Direct-acting agonists

Adrenergic agonist

Cholinergic agonist
  Indirect-acting agonist: Excites the
nerve fiber

release of transmitter prevents the reuptake of

neurotransmitter

 Adrenergic indirect-acting agonists, eg:

Hydroxyamphetamine,
Cocaine
 Cholinergic indirect-acting agonists, eg: Physostigmine
Adrenergic

Cholinergic
 Indirect-acting agonists -Adrenergic

Hydroxyamphetamine

Cocaine
 Indirect-acting agonist - Cholinergic

Action of Acetylcholinesterase (AChe)

Action of Physostigmine
  Antagonists: Either block the receptor sites or block the release of the
neurotransmitter, thus preventing action of the effector.
 Adrenergic antagonists, eg: Dapiprazole
 Cholinergic antagonists , eg: Atropine, cyclopentolate, and
tropicamide

Antagonists

Adrenergic antagonist

Cholinergic antagonist