Therapeutic Potential of Secreted Molecules Derived from Human Amniotic Fluid Mesenchymal Stem/Stroma Cells in a Mice Model of Colitis.

Inflammatory bowel diseases (IBDs) are the result of pathological immune responses due to environmental factors or microbial antigens into a genetically predisposed individual. Mainly due to their trophic properties, a mounting interest is focused on the use of human mesenchymal stem/stromal cells (hMSCs) to treat IBD disease in animal models. The aim of the study is to test whether the secreted molecules, derived from a specific population of second trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped MSCs (SS-AF-MSCs), could be utilized as a novel therapeutic, cell free approach for IBD therapy. Induction of colitis was achieved by oral administration of dextran sulphate sodium (DSS) (3 % w/v in tap water), for 5 days, to 8-week-old NOD/SCID mice. The progression of colitis was assessed on a daily basis through recording the body weight, stool consistency and bleeding. Conditioned media (CM) derived from SS-AF-MSCs were collected, concentrated and then delivered intraperitoneally into DSS treated mice. To evaluate and determine the inflammatory cytokine levels, histopathological approach was applied. Administration of CM derived from SS-AF-MSCs cells reduced the severity of colitis in mice. More importantly, TGFb1 protein levels were increased in the mice received CM, while TNFa and MMP2 protein levels were decreased, respectively. Accordingly, IL-10 was significantly increased in mice received CM, whereas TNFa and IL-1b were decreased at mRNA level. Our results demonstrated that CM derived from SS-AF-MSCs cells is able to ameliorate DSS-induced colitis in immunodeficient colitis mouse model, and thus, it has a potential for use in IBD therapy.

Effects of an early experience of reward through maternal contact or its denial on the dopaminergic system of the rat brain.

The mesolimbic/mesocortical dopaminergic pathway plays a pivotal role in the reward system. During the neonatal period the mother is the main source of rewarding stimuli. We have developed an experimental model in which rat pups learn a T-maze during the neonatal period (postnatal day (PND) 10-13) using contact with the mother as the reward. One group of animals is allowed contact with the mother (receipt of expected reward, RER) while the other was denied (denial of expected reward, DER). We determined the effects of these two early experiences in the prefrontal cortex (PFC) and the nucleus accumbens (nAc), the levels of dopamine (DA) and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] by high-performance liquid chromatography and those of D1 and D2 receptors by autoradiographic in vitro binding both on PND 13 and in adulthood. On PND13, 2h after the end of training, the RER experience resulted in higher DA, HVA and D1 receptor levels in the nAc, while the DER in lower DA and its metabolites (DOPAC and HVA) in the PFC. These results could be related to the reward the RER pups received through the contact with their mother. The RER and DER early experience had long-term sex-dependent effects: The RER-induced activation of the dopaminergic system in the nAc was also evident in adult female rats. In contrast, adult DER males, similar to PND13 animals, had reduced dopamine in the PFC. Our results document that early experiences, a key determinant of adult brain function, affect the dopaminergic system which is disturbed in many psychiatric diseases.

Optical coherence tomography in the study of the Goldmann-Favre syndrome.

PURPOSE: To report a case of Goldmann-Favre syndrome with special emphasis on the optical coherence tomography findings. METHODS: In a 23-year-old white man with an 8-year history of visual impairment in both eyes and night blindness, vertical and horizontal optical coherence tomography images were obtained through the macula and through the retinoschisis located at the temporal side of the macula. RESULTS: Optical coherence tomography showed in the left eye a clear loss of the inner retinal layer at the fovea and the formation of inner and outer retinal layer holes in the temporally located retinoschisis. The outer retinal layer hole had rolled edges. CONCLUSION: In Goldmann-Favre syndrome, optical coherence tomography demonstrated confluent macular cystoid changes and retinoschisis in both eyes. In the left eye, a lamellar macular hole and retinoschisis with inner retinal layer and outer retinal layer holes were observed. The outer retinal layer hole had rolled edges.

Visual field improvement after treatment of optic disk pit maculopathy with the macular buckling procedure.

PURPOSE: To evaluate visual field changes in 18 of 21 patients with unilateral optic disk pit maculopathy who were successfully treated with the macular buckling procedure. METHODS: In this prospective study, visual field examination with the Humphrey analyzer (programs 30-2 and 10-2) was recorded before treatment, repeated 1 month after the operation, and repeated every 6 months thereafter. All 18 patients were treated with the macular buckling procedure. The operation consisted of fixation of a silastic sponge explant at the posterior pole corresponding to the macula. RESULTS: In 18 eyes included in the study and successfully treated, an improvement in visual field indices was recorded. The mean deviation improved from -7.75+/-3.15 (program 30-2) and -10.19+/-3.66 (program 10-2) decibels before surgery to -6.25+/-2.61 (P<0.0001) and -8.56+/-3.13 (P<0.0001) decibels at the last examination, respectively. No additional visual field defect was induced in any of the 18 eyes after treatment. Also, the majority of the eyes (16/18) gained from 1 to 7 Snellen lines of visual acuity (P<0.0001). CONCLUSION: Improvement of central and peripheral visual field (within 30 degrees of fixation) was recorded after the treatment of optic disk pit maculopathy with the macular buckling procedure. This technique seems to be effective for treatment of the disease with good anatomic and functional results.

Fluorescein and indocyanine green angiographic findings in congenital optic disk pit associated with macular detachment.

PURPOSE: To investigate the pattern of congenital optic disk pits associated with maculopathy using indocyanine green angiography (ICG) and fluorescein angiography (FA). METHODS: Seventeen consecutive patients with unilateral congenital optic disk pit complicated by maculopathy were prospectively enrolled in the study. Complete ophthalmologic examination, color stereophotography, red-free photography, FA, and ICG angiography were performed on all patients during their first examination in our department. RESULTS: Absolute hypofluorescence of the optic disk pit was noted in all eyes on ICG angiography. On the contrary, all eyes showed early hypofluorescence and late staining of the optic pit on FA. All 17 eyes presented a delineated late hyperfluorescence corresponding to the area of macular elevation on both ICG angiography and FA. The intensity of the hyperfluorescence was milder in cases with long-standing maculopathy. CONCLUSION: Imaging of congenital optic disk pits associated or not with macular elevation using ICG angiography has not been reported in the literature. The increased hyperfluorescence in the late phases of the macular elevation in the studied eyes could be attributed to leakage of indocyanine or fluorescein dye into the schisis cavity and the subretinal fluid.

Cyst formation in optic disc pit maculopathy.

PURPOSE: To evaluate the presence and the evolution of cyst formation in optic disc pit maculopathy. METHODS: In this prospective study, 18 cases with optic disc pit maculopathy were studied. Five of them showed cyst formation in the fovea at the initial examination. The fundus findings were documented with slit-lamp biomicroscopy, indirect ophthalmoscopy, and stereoscopic photography of the posterior pole. All 5 patients were treated with a macular scleral buckle procedure. RESULTS: The presence of cysts in the elevated macula depends on the grade of the disease. Cyst formation can develop not only in the later stage of the disease but also quite early. In all 5 patients cyst formation gradually decreased and finally disappeared after the surgical procedure. CONCLUSIONS: Cyst formation is an entity which accompanies the macular detachment associated with optic disc pit. The development of the cysts has been noticed after the establishment of the schisis-like separation and before or in conjunction with the formation of a lamellar macular hole which usually accompanies the optic disc pit maculopathy.

Retinal vascular involvement in acute toxoplasmic retinochoroiditis.

The present study deals with the retinal vascular involvement in 64 patients with toxoplasmic retinochoroiditis during the acute phase of the disease and its evolution. Vascular involvement was noted in all 64 eyes during the acute phase of the disease. In 59 (92%) out of 64 cases the vascular involvement was located in the same retinal quadrant as the active toxoplasmic lesion. In the remaining 5 eyes (8%) the vascular participation was found in all four retinal quadrants. In 3 (5%) out of 64 cases, the vascular infiltration was extremely severe and resulted in retinal vascular obstruction. In all three cases the vessel traversed the active toxoplasmic lesion. In 35 (55%) out of 64 patients the initial vascular picture changed in the course of the acute phase of the disease. In these patients, the lesions had extended to the adjacent vessels or to other parts of the involved vessel. In the further course of the evolution of the active toxoplasmic lesion, the vascular involvement did not persist indiscriminately. It was noted that in 14 (22%) out of 64 cases the vascular lesions gradually regressed and eventually disappeared together with the active toxoplasmic lesion and the formation of the retinochoroidal scar. In the remaining 50 (78%) out of 64 cases the vascular involvement either disappeared after the establishment of the retinochoroidal scar in 3-12 months (29 cases) or remained permanently (21 cases).

Long-term study of patients with congenital pit of the optic nerve and persistent macular detachment.

During the period 1970-87 we evaluated the changes of the optic disc, peripapillary area, detached macula and visual acuity in 16 cases with congenital pit of the optic nerve and macular detachment. The study revealed in 9 of the 16 cases (56%) an increase of the dimension of the pit or changes in its color, findings which were directly related to the duration of the macular detachment. Chorioretinal scarring, pigment migration, or both, were also noted mainly at the temporal margin of optic disc. In 5/16 cases we found during the follow-up an extension of macular elevation. In altogether 10 out of 16 cases the retinal elevation covered the larger portion of the mid-periphery temporally. In 7/16 cases the final visual acuity remained unchanged, in 9/16 cases deteriorated. The difference, however, in the latter 9 cases between initial and final visual acuity was negligible. During the follow-up period deterioration of the visual fields was also noted.

Cilioretinal arteries in conjunction with a pit of the optic disc.

Cilioretinal arteries were noted to accompany pits of the optic disc in 16 of 25 cases (64%). Fourteen of the 16 cases were found to have 2 cilioretinal arteries (86%). The cilioretinal arteries were directly related to the pit of the disc and emerged either from the bottom or the margin of the pit in a proportion of 86%. This finding reinforces the assumption that the optic disc pit belongs to the same spectrum of congenital anomalies which also includes optic disc coloboma, megalopapilla and morning glory syndrome. A fluorescein angiography study showed hyperfluorescence of the pit in 12/16 cases and in particular in all the cases in which both cilioretinal arteries emerged from the pit. Hypofluorescence was noted in 7/9 cases in which the pit was not associated with cilioretinal arteries. Our findings could support the view that hyperfluorescence of the pit, which is not a constant phenomenon, mostly depends on the presence of cilioretinal arteries emerging from the pit.