Thursday, May 26, 2011

Abstracte: Phospholipid transfer protein and the tear fluid

Dry Eye Symptoms Are Increased in Mice Deficient in Phospholipid Transfer Protein (PLTP).

In the tear fluid the outermost part facing the tear-air interface is composed of lipids preventing evaporation of the tears. Phospholipid transfer protein (PLTP) mediates phospholipid transfer processes between serum lipoproteins and is also a normal component of human tears. To study whether PLTP plays any functional role in tear fluid we investigated PLTP-deficient mice, applying functional and morphologic analyses under normal housing and experimentally induced dry eye conditions. Aqueous tear fluid production, corneal epithelial morphology, barrier function, and occludin expression were assessed. In mice with a full deficiency of functional PLTP enhanced corneal epithelial damage, increased corneal permeability to carboxyfluorescein, and decreased corneal epithelial occludin expression were shown. These pathologic signs were worsened by experimentally induced dry eye both in wild-type and PLTP knock-out mice. Deficiency in the production of tear PLTP in mice is accompanied by corneal epithelial damage, a feature that is typical in human dry eye syndrome (DES). To complement animal experiments we collected tear fluid from human dry eye patients as well as healthy control subjects. Increased tear fluid PLTP activity was observed among DES patients. In conclusion, the presence of PLTP in tear fluid appears to be essential for maintaining a healthy and functional ocular surface. Increased PLTP activity in human tear fluid in DES patients suggests an ocular surface protective role for this lipid transfer protein.

Am J Pathol. 2011 May;178(5):2058-65.
Setälä NL, Metso J, Jauhiainen M, Sajantila A, Holopainen JM.
Department of Ophthalmology, University of Helsinki, Helsinki, Finland; Department of Ophthalmology, University of Turku, Finland; National Institute for Health and Welfare and Institute for Molecular Medicine, Biomedicum, Helsinki, Finland.

Abstract: Dry eye in GvHD

Looks at frequency of dry eye and other ocular complications from chronic GvHD in a patient population in Pakistan.

Frequency of ocular manifestations of chronic graft versus host disease.

With the advancement of techniques for haematopoietic cell transplantation, the number of transplant survivors is increasing rapidly and so are the chances of chronic graft versus host disease (cGVHD). The ocular manifestations of this disease have not been explored in our local population. This study was conducted to determine the frequency of ocular complications in cases of cGVHD following successful bone marrow transplantation.

Twelve diagnosed cases of cGVHD were evaluated from June 2008 to March 2009 and there ocular manifestations were noted especially the ocular surface disorders, using double staining method with fluorescein and rose-bengal.

Nine patients (75%) were having dry eyes, 7 (58.3%) with mebomian glands dysfunction, 4 (33%) with acute conjunctivitis, 2 (16.7%) with bilateral lacrimal canalicular occlusion, and 1 (8.3%) each of bilateral posterior subcapsular cataract, unilateral sterile corneal epithelial defect, anterior uveitis, retinal haemorrhages and disc oedema.

The higher frequency of dry eyes along with other ocular manifestations in patients of cGVHD suggests the need of close ophthalmic monitoring in all such cases.

J Ayub Med Coll Abbottabad. 2010 Jan-Mar;22(1):80-3.
Arain MA, Niazi MK, Khan MD, Ahmed P, Naz MA, Fayyaz M.
Armed Forces Institute of Ophthalmology, Rawalpindi.

Abstract: Mouse lacrimal cell study

I'm not going to attempt to summarize something this technical, but I do love this sort of thing. When i'm done tripping over the terminology and prowling through wikipedia to get a better sense of it, I'm just in such awe of the complexity and beauty of our tear production system. We are fearfully and wonderfully made.

Polycystin-2 expression and function in adult mouse lacrimal acinar cells.

Lacrimal glands regulate the production and secretion of tear fluid. Dysfunction of lacrimal gland acinar cells can ultimately result in ocular surface disorders, such as dry-eye disease. Ca(2+) homeostasis is tightly regulated in the cellular environment, and secretion from the acinar cells of the lacrimal gland is regulated by both cholinergic and adrenergic stimuli, which both result in changes in the cytosolic Ca(2+) concentration. We have previously described the detailed intracellular distribution of IP(3)Rs and RyRs in lacrimal acinar cells, however, little is known regarding the expression and distribution of the third major class of intracellular Ca(2+) release channels, transient receptor potential polycystin family (TRPP) channels.

Studies were performed in adult lacrimal gland tissue of Swiss-Webster mice. Expression, localization and intracellular distribution of TRPP Ca(2+) channels were investigated using immunocytochemistry, immunohistochemistry and electron microscopy. The biophysical properties of single polycystin-2 channels were investigated using a planar lipid bilayer electrophysiology system.

All channel-forming isoforms of TRPP channels (polycystin-2, polycystin-L and polycystin-2L2) were expressed in adult mouse lacrimal gland. Subcellular analysis of immunogold labeling revealed strongest polycystin-2 expression on the membranes of the endoplasmic reticulum, Golgi and nucleus. Biophysical properties of lacrimal gland polycystin-2 channels were similar to those described for other tissues.

The expression of TRPP channels in lacrimal acinar cells suggests a functional role of the proteins in the regulation of lacrimal fluid secretion under physiological and disease conditions, and provides the basis for future studies focusing on physiology and pharmacology.

Invest Ophthalmol Vis Sci. 2011 Apr 20. [Epub ahead of print]
Kaja S, Hilgenberg JD, Rybalchenko V, Medina-Ortiz WE, Gregg EV, Koulen P.
Vision Research Center and Departments of Ophthalmology and Basic Medical Science, University of Missouri - Kansas City, School of Medicine, Kansas City, MO.

Wednesday, May 25, 2011

Abstract: Reduced goblet cell density in dry eye patients

This study, originating in Nepal of all places, is not original and not news, but it's a useful reminder that dry eyes are not just about meibomian and/or lacrimal gland dysfunction. There's the mucin issue as well - which depends on goblet cell density. Of late most of the chatter and technological developments seem to be focused on the meibomian glands. They are nice low hanging fruit (so to speak) and it's easy to understand why treating them has come into vogue. It's not really all that hard to get clinical improvement, at the end of the day. And the attention MGs are getting truly is long overdue.

And yet...

Where oh where is the PAIN coming from? When I think of the people doing all these glamorous boutique MGD treatments and not experiencing conclusive, lasting symptomatic improvement it makes me gnash my teeth.

We still really don't know our chickens from our eggs in the world of dry eye. Let's keep goblet cells and mucous in mind.

The conjunctival impression cytology between the diagnosed cases of dry eye and normal individuals.

The dry eye or tear film dysfunction is a common ophthalmic syndrome.

To compare the results of conjunctival impression cytology between dry eye patients and normal individuals.

Subjects and methods:
A case control study including consecutive cases of dry eye syndrome was carried out. Individuals without dry eye were taken as control. Impression of conjunctiva with cellulose acetate filter paper was taken from inferonasal bulbar conjunctiva and was stained with Periodic Acid- Schiff (PAS) and counter-stained with haematoxylin and eosin. Main outcome measure: goblet cell density.

There was a female preponderance in dry eye disease. Of 114 dry eye cases, 49.2% eyes showed decreased or absent goblet cell density. In 72 normal individuals 73.7% eyes showed normal goblet cell density and 26.3% of eyes showed decreased or absent goblet cells (p less than 0.001). The tear break-up time (TBUT) test was significantly more likely to be less than 10 seconds in cases as compared to the controls ( OR = 19.36, 95% CI = 7.56 - 52.52). Similarly, the goblet cell density was likely to be significantly reduced in cases with dry eye syndrome (OR= 2.25, 95% CI = 1.26 - 4.02, p = 0.003).

Goblet cell density significantly reduces in dry eye syndrome. The impression cytology is a useful test for the diagnosis of dry eye syndrome. Key words: impression cytology; conjunctiva; dry eyes; tear film.

Nepal J Ophthalmol. 2011 Jan;3(5):39-44. doi: 10.3126/nepjoph.v3i1.4277.
Shrestha E, Shrestha JK, Shayami G, Chaudhary M.
Consultant Ophthalmologist, Himalaya Eye Hospital, Pokhara, Nepal.