Prediction of long-term visual outcome of idiopathic full-thickness macular hole surgery using optical coherence tomography parameters that estimate potential preoperative photoreceptor damage.

PURPOSE: To identify optical coherence tomography (OCT) parameters that predict postoperative best corrected visual acuity (BCVA) and are based on recent understanding of the pathomechanism of idiopathic full thickness macular hole (iFTMH) formation and closure. METHODS: A retrospective consecutive case series of patients who had macular hole (MH) surgery at our institution between 2016 and 2022 was performed. 32 eyes of 30 patients were selected with at least 12 months of follow-up, closed MH and good quality OCT at each visit. Univariate correlation analysis, multiple logistic regression with forward stepwise selection, and Akaike's Information Criterion (AIC) were used to identify the best predictors for postoperative BCVA at 6 and 12 months (M), and final (≥ 12 M) visits, and a new OCT index was created. Abilities of best models/indices to predict < 0.30 logMAR (> 20/40) BCVA were compared to macular hole index (MHI) using the area under the receiver operating curve (AU-ROC) analysis. RESULTS: Statistical analysis revealed base diameter (B) (6 M), preoperative BCVA and B (12 M) and smaller ELM-GCL distance (A), and B (final visit) as predictors for postoperative BCVA. AU-ROC analysis indicated greatest AUC at 6 M for MHI and B (0.797, p = 0.004 and 0.836 p = 0.001, respectively) and for the new A/B index at 12 M and final visit (0.844, p = 0.002 and 0.913, p = 0.003, respectively). CONCLUSION: Our study suggests that MHI and B can be useful predictors of short term BCVA while the new A/B index that incorporates OCT parameters indicating potential preoperative photoreceptor damage may be a good predictor for long term postoperative BCVA. Our findings support the theory that initial hole formation mechanisms and photoreceptor damage define visual prognosis.

Analysis of the Association between Retinal Artery Occlusion and Acute Ischaemic Stroke/ST-Elevation Myocardial Infarction and Risk Factors in Hungarian Patients.

Background and Objectives: We aimed to analyse data on retinal artery occlusion (RAO) patients to explore correlations with acute ischaemic stroke (AIS), ST-elevation myocardial infarction (STEMI), and cardio/cerebrovascular comorbidities. Patients and Methods: Our retrospective cohort study included 169 RAO and 169 age- and gender-matched control patients. We examined the association of AIS, STEMI, and related comorbidities such as hypertension (HT), type 1 and type 2 diabetes (T1DM and T2DM, respectively), hyperlipidaemia, and ischaemic heart disease (IHD) with RAO. We also recorded atrial fibrillation in our RAO patients. Results: Our results demonstrated that RAO patients developed both AIS and STEMI at a significantly higher rate compared to controls (p < 0.001 for both). We also found that RAO patients had a significantly higher prevalence of HT and hyperlipidaemia (p1 = 0.005, p2 < 0.001) compared to controls. Multiple risk factors together significantly increased the odds of developing AIS and STEMI. Conclusions: Our results suggest that through identifying and treating the risk factors for RAO patients, we can reduce the risk of AIS, STEMI, and RAO of the fellow eye. Considering that ophthalmologists are often the first detectors of these cardiovascularly burdened patients, collaboration with colleagues from internal medicine, cardiology, and neurology is essential to achieve secondary prevention.

Different Effects of Cigarette Smoke, Heated Tobacco Product and E-Cigarette Vapour on Orbital Fibroblasts in Graves' Orbitopathy; a Study by Real Time Cell Electronic Sensing.

Thyroid autoimmunity in Graves' disease (GD) is accompanied by Graves' orbitopathy (GO) in 40% of the cases. Orbital fibroblasts (OF) play a key role in the pathogenesis and cigarette smoking is a known deteriorating factor. Alongside conventional cigarettes (CC) new alternatives became available for smokers, including heated tobacco products (HTP) and E-cigarettes (ECIG). We aimed to study the cellular effects of smoke extracts (SE) in orbital fibroblasts. Primary OF cultures from GO and NON-GO orbits were exposed to different concentrations of SE (1%, 50%) and the changes were followed using Real Time Cell Electronic Sensing (RT-CES). Untreated GO and NON-GO cells had different maximum cell index (CI) values of 3.3 and 2.79 respectively (p < 0.0001). CC, HTP and ECIG treated NON-GO fibroblasts exhibited peak CIs of 2.62, 3.32 and 3.41 while treated GO cells' CIs were higher, 5.38, 6.25 and 6.33, respectively (p < 0.0001). The metabolic activity (MTT) decreased (p < 0.001) and hyaluronan production doubled (p < 0.02) after 50% of CC SE treatment in all cell cultures. GO fibroblasts were more sensitive to low concentration SE then NON-GO fibroblasts (p < 0.0001). The studied SEs exerted different effects. RT-CES is a sensitive technique to detect the effects of very low concentration of SE on fibroblasts.

Unusual onset of thyroid associated orbitopathy during pregnancy: case report and review of literature.

BACKGROUND: Thyroid associated orbitopathy (TAO) is the most common extrathyroidal complication of Graves' disease. The disease course ranges from mild, where symptomatic therapy is sufficient, to severe, where high dose steroid administration or orbital decompression surgery is required. Women of their reproductive age are more likely to be affected. Although pregnancy is a state of enhanced immune tolerance, TAO may develop or worsen in 0.2-0.4% of pregnant women. CASE PRESENTATION: We present the case of a 19-year-old woman who has developed hyperthyroidism and progressive TAO during the second trimester of her third pregnancy, which has improved postpartum. The possible mechanisms and the importance of follow up in pregnancy is discussed. CONCLUSIONS: Expectant mothers with Graves' disease require follow up of eye signs throughout pregnancy, preferably in the setting of a thyroid-eye clinic.

Correction of irregular and induced regular corneal astigmatism with toric IOL after posterior segment surgery: a case series.

BACKGROUND: Toric intraocular lens (IOL) implantation can be an effective method for correcting corneal astigmatism in patients with vitreoretinal diseases and cataract. Our purpose is to report the outcome of toric IOL implantation in two cases - a patient with scleral-buckle-induced regular corneal astigmatism and a patient with keratoconus following pars plana vitrectomy. As far as we are aware, there are no reported cases of toric IOL implantation in a vitrectomized eye with keratoconus nor of toric IOL implantation in patients with scleral-buckle-induced regular corneal astigmatism. CASE PRESENTATION: Two patients with myopia and high corneal astigmatism underwent cataract operation with toric IOL implantation after posterior segment surgery. Myopia and high astigmatism (>2.5 diopter) were caused by previous scleral buckling in one case and by keratoconus in the other case. Pre- and postoperative examinations during the follow-up of included uncorrected and spectacle corrected distance visual acuity (UCDVA/CDVA), automated kerato-refractometry (Topcon), Pentacam HR, IOL Master (Zeiss) axial length measurements and fundus optical coherence tomography (Zeiss). One year postoperatively, the UCDVA and CDVA were 20/25 and 20/20 in both cases, respectively. The absolute residual refractive astigmatism was 1.0 and 0.75 Diopters, respectively. The IOL rotation was within 3° in both eyes, therefore IOL repositioning was not necessary. Complications were not observed in our cases. CONCLUSION: These cases demonstrate that toric IOL implantation is a predictable and safe method for the correction of high corneal astigmatism in complicated cases with different origins. Irregular corneal astigmatism in keratoconus or scleral-buckle-induced regular astigmatisms can be equally well corrected with the use of toric IOL during cataract surgery. Previous scleral buckling or pars plana vitrectomy seem to have no impact on the success of the toric IOL implantation, even in keratoconus. IOL rotational stability and refractive predictability in patients with a previous vitreoretinal surgery can be as good as in uncomplicated cases.

Association between mediators in the tear fluid and the severity of keratoconus.

PURPOSE: To study the association between different types of mediators in the tear fluid and topographic indices characterizing the severity of keratoconus (KC). METHODS: In this study, nonstimulated tear fluid samples were collected from 14 eyes of 11 patients with KC. The following indices were measured by corneal topography: maximum K value, average K value, Klyce/Maeda keratoconus index (KCI), Smolek/Klyce keratoconus severity index, opposite sector index, center/surround index, keratoconus prediction index and standard deviation of corneal power. The concentrations of interleukin (IL)-6, IL-13, CXCL8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5, regulated and normal T cell expressed and secreted), matrix metalloproteinase-9 (MMP-9), MMP-13, tissue inhibitor of metalloproteinase-1, nerve growth factor (NGF) and epidermal growth factor were measured by cytometric bead array technology. Release of mediators was calculated from their concentrations and the volume of tears collected over 2 min. RESULTS: Significant positive associations were found between CCL5, MMP-13 and NGF and several topographic indices. Significant negative correlations were found between IL-6 and KCI. Age-dependent associations were observed between IL-13, CXCL8, CCL5 and MMP-13 and the topographic data. CONCLUSION: Several correlations were observed between the mediators and the topographic indices, suggesting possible roles in the pathophysiology of KC. Our data indicate that some mediators have different effects on the severity of disease in an age-dependent manner.

Effect of contact lens wear on the release of tear mediators in keratoconus.

OBJECTIVES: The release of different cytokines and mediators in tears of patients with keratoconus (KC) wearing contact lenses (CLs) may contribute to the pathology of KC. METHODS: Cohort study was established in patients with KC wearing rigid gas permeable (RGP) CL (group I), patients with ametropia wearing silicone hydrogel (Si-Hi) CL (group II) and ametropic patients wearing RGP CL (group III). RESULTS: Our findings indicate that before CL wear, the release of epidermal growth factor (EGF) and tissue-type plasminogen activator (t-PA) was attenuated, whereas matrix metalloproteinase (MMP)-9, interleukin (IL)-6, chemokine (C-C motif) ligand 5 (CCL5), IL-13, and plasminogen activator inhibitor (PAI)-1 were enhanced in KC compared with ametropes. An increasing linear trend over time was found for MMP-9, EGF, and CXCL8 in KC and MMP-9, MMP-13, IL-6, and CXCL8 in group III. Significant differences were observed in the linear trend over time between groups I and III for MMP-13 and tissue inhibitor of metalloproteinases (TIMP)-1; between groups I and II for MMP-9 and CXCL8; and between groups III and II for MMP-9, CXCL8, and MMP-13. In KC, the release of MMP-9 at week 6 and nerve growth factor (NGF) at 10 min was higher, but NGF at week 2 was lower than that in group II. The release of MMP-13 and NGF at week 2 and 6 were lower in the KC group as compared with group III, and similarly, with IL-6 and CXCL8 at week 2 and PAI at all time points. CONCLUSIONS: Contact lens wear can influence the levels and dynamics of various mediators in the tears of patients with KC that might have an impact on the progression of the disease.

[Autologous neurosensory retinal transplantation.] / Autológ neuroszenzoros retinatranszplantáció.

Macular hole is a full-thickness neuroretinal defect in the fovea. The surgical solution is the removal of the internal limiting membrane (ILM) during vitrectomy with gas filling. Several surgical techniques have been described for the closure of refractory macular holes (about 5%), that reappear after successful surgery or do not close despite surgery. This article presents the first autologous neurosensory retina transplantation performed in Hungary for a large, refractory, full-thickness macular hole, with a brief overview of macular hole surgery. In September 2022, we performed a combined phacovitrectomy with ERM/ILM peeling and SF6 gas filling due to cataract, epiretinal membrane (ERM), and large macular hole due to the deterioration of vision in our patient's left eye for months, with a visual acuity of 6%. We drew the patient's attention to the importance of postoperative head positioning, which she ignored. With a visual acuity of 4%, due to a refractive macular hole (at the base: 983 µm, at the smallest diameter: 609 µm), on December 14, 2022, autologous neurosensory retina transplantation was performed using intraoperative OCT (Zeiss ARTEVO 800). At the end of the surgery, decalin was left in the eye to keep the graft in place, and the patient spent 5 days in a supine position. The decalin was removed with another operation, followed by C3F8 gas filling. 8 weeks after surgery, we documented a closed macular hole with 20% visual acuity, which was stable during the 6-month follow-up. Among the options considered for the resolution of refractory macular holes, autologous neurosensory retinal transplantation, which results in a visual improvement of our patient, is an intervention worth considering. Intraoperative OCT was a great help in performing the surgery. Although the decalin left temporarily in the eye helps to keep the transplant in place, it requires a continuous supine position and another operation is essential to remove it. Further experience is needed to establish the exact indication for autologous neurosensory retinal transplantation. Orv Hetil. 2023; 164(38): 1511-1517.

High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice.

OBJECTIVE: The CACNA1A gene encodes the pore-forming subunit of neuronal Ca(V)2.1 Ca2+ channels. In patients, the S218L CACNA1A mutation causes a dramatic hemiplegic migraine syndrome that is associated with ataxia, seizures, and severe, sometimes fatal, brain edema often triggered by only a mild head trauma. METHODS: We introduced the S218L mutation into the mouse Cacna1a gene and studied the mechanisms for the S218L syndrome by analyzing the phenotypic, molecular, and electrophysiological consequences. RESULTS: Cacna1a(S218L) mice faithfully mimic the associated clinical features of the human S218L syndrome. S218L neurons exhibit a gene dosage-dependent negative shift in voltage dependence of Ca(V)2.1 channel activation, resulting in enhanced neurotransmitter release at the neuromuscular junction. Cacna1a(S218L) mice also display an exquisite sensitivity to cortical spreading depression (CSD), with a vastly reduced triggering threshold, an increased propagation velocity, and frequently multiple CSD events after a single stimulus. In contrast, mice bearing the R192Q CACNA1A mutation, which in humans causes a milder form of hemiplegic migraine, typically exhibit only a single CSD event after one triggering stimulus. INTERPRETATION: The particularly low CSD threshold and the strong tendency to respond with multiple CSD events make the S218L cortex highly vulnerable to weak stimuli and may provide a mechanistic basis for the dramatic phenotype seen in S218L mice and patients. Thus, the S218L mouse model may prove a valuable tool to further elucidate mechanisms underlying migraine, seizures, ataxia, and trauma-triggered cerebral edema.

Corneal transplantation in Hungary (1946-2009).

BACKGROUND: To identify changing trends in indications for corneal transplantation in Debrecen, Hungary over the past 64 years. DESIGN: Retrospective study, at the Department of Ophthalmology, University of Debrecen, Hungary. PARTICIPANTS: Four thousand seven hundred and seventy-eight patients who underwent keratoplasty. METHODS: The analysis was based on medical charts, surgical descriptions and eye bank records. MAIN OUTCOME MEASURES: Keratoplasty indications between January 1946 and December 2009. For an easier overview, the 64-year interval was divided into seven time periods (1946-1955, I; 1956-1965, II; 1966-1975, III; 1976-1985, IV; 1986-1995, V; 1996-2005, VI; 2006-2009, VII). RESULTS: Over the 64 years, clinical indications for keratoplasty were corneal scarring (24.9%), regraft (18.6%), keratoconus (18.6%), pseudophakic/aphakic corneal oedema (12%), stromal corneal dystrophies (6%), non-infectious keratitis (4.7%), chemical injuries (3.3%), corneal degenerations (3%), mechanical trauma (1.7%), infectious keratitis (1.4%), endothelial corneal dystrophies (1.3%) and others (4.5%). During periods I-IV, corneal scarring was the most common indication for corneal transplantation. In period V, corneal ectasia became the leading clinical indication. Regraft was the most frequent indication in period VI. In the most recent years, an emerging tendency in pseudophakic/aphakic corneal oedema as the indication for keratoplasty was observed. CONCLUSIONS: In Hungary, the number of grafts has increased greatly in the past 64 years, the transplantation rates are similar to those of industrial countries. Indications for corneal transplantation have changed considerably over the last half decade from corneal scarring to corneal ectasia, regraft and pseudophakic/aphakic corneal oedema.

Tear Mediators NGF along with IL-13 Predict Keratoconus Progression.

Purpose: To find immunomediator combinations which could sensitively indicate keratoconus progression.Methods: Tear samples of 42 patients with keratoconus were collected at baseline and at the end of a one-year follow-up. The concentrations of 13 mediators were measured by CBA. Based on Pentacam HR examination, eyes were divided into a non-progressive and a progressive group.Results: At the end of the follow-up, significant differences were observed in the release of IFNγ, IL-13, IL-17A, CCL5, MMP-13 and PAI-1 between the two groups. Changes in five Pentacam parameters correlated positively with changes in IFNγ, IL-13, IL-17A, CXCL8, CCL5, TIMP-1 and t-PA. We found that tear level of IL-13 in combination with NGF can predict the progression of keratoconus with 100% specificity and 80% sensitivity.Conclusion: The findings of our longitudinal study may underscore the importance of NGF and IL-13 tear levels in the prediction of keratoconus progression.

Effects of aging on corneal parameters measured with Pentacam in healthy subjects.

Our purpose was to prospectively analyze the age-related changes of corneal Scheimpflug parameters in healthy subjects. Thirty-five eyes of 35 volunteers (age 14-67 years) were investigated with an average interval of 3.6 years. Changes of corneal parameters (flattest keratometric reading at anterior (K1F) and posterior surface (K1B), steepest keratometric reading at anterior (K2F) and posterior surface, anterior astigmatism, posterior astigmatism (AstigB), flat axis of anterior and posterior astigmatism (AxisB), thinnest pachymetric value (PachyMin), corneal volume (CV10-mm)) were analyzed. K1F and K2F decreased significantly during observation and showed stronger decrease in younger than in older individuals. Higher values proved to be more stable. K1B decreased significantly and the degree of decrease was dependent on its baseline value and age: in young subjects low values increased, high values decreased. AstigB decreased significantly and showed a baseline-dependent significant increase from lower and a significant decrease from higher initial values. Over time, the mean AxisB shifted significantly. PachyMin and CV decreased significantly with age, especially from higher baseline values in younger subjects. The results of this longitudinal study suggest that both corneal surfaces change significantly with age. We demonstrate for the first time that age and baseline values influence age-related changes of corneal parameters.

Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats.

We proposed that inhibition of mitochondrial adenine nucleotide translocator (ANT) by long chain acyl-CoA (LCAC) underlies the mechanism associating obesity and type 2 diabetes. Here we test that after long-term exposure to a high-fat diet (HFD): (i) there is no adaptation of the mitochondrial compartment that would hinder such ANT inhibition, and (ii) ANT has significant control of the relevant aspects of oxidative phosphorylation. After 7 weeks, HFD induced a 24+/-6% increase in hepatic LCAC concentration and accumulation of the oxidative stress marker N(epsilon)-(carboxymethyl)lysine. HFD did not significantly affect mitochondrial copy number, oxygen uptake, membrane potential (Deltapsi), ADP/O ratio, and the content of coenzyme Q(9), cytochromes b and a+a(3). Modular kinetic analysis showed that the kinetics of substrate oxidation, phosphorylation, proton leak, ATP-production and ATP-consumption were not influenced significantly. After HFD-feeding ANT exerted considerable control over oxygen uptake (control coefficient C=0.14) and phosphorylation fluxes (C=0.15), extra- (C=0.23) and intramitochondrial (C=-0.56) ATP/ADP ratios, and Deltapsi (C=-0.11). We conclude that although HFD induces accumulation of LCAC and N(epsilon)-(carboxymethyl)lysine, oxidative phosphorylation does not adapt to these metabolic challenges. Furthermore, ANT retains control of fluxes and intermediates, making inhibition of this enzyme a more probable link between obesity and type 2 diabetes.

Neonatal food restriction permanently alters rat body dimensions and energy intake.

Neonatal food restriction (FR) in rats, by means of increased litter size, has been used as a model for developmental programming by several investigators. However, the results reported have been inconsistent and difficult to compare between studies. In the present study, we aim to characterize the effects of this model throughout life in both sexes of one particular strain. On the second day of life, Wistar rat pups were randomly assigned to a litter of 10 (control) or 20 (FR). All litters had an equal number of males and females, and pups were weaned on day 25. Body dimensions and food intake were measured regularly until the age of one year. Serum leptin levels were determined in four subsets of different ages. FR acutely reduced growth in all body dimensions and serum leptin levels. Despite catch-up after weaning, all these parameters remained reduced throughout life. Male and female FR rats had a significantly reduced absolute energy intake throughout life. Male FR rats had significantly higher energy intake adjusted for body weight immediately after weaning. During catch-up growth, both FR males and females showed significantly enhanced feed efficiency. These results suggest that neonatal food restriction programmed both male and female Wistar rats to remain small and lean in adult life, with a lower food intake. Low neonatal leptin levels may play a mechanistic role in this process.

Relative anterior microphthalmos in oculodentodigital dysplasia.

Here, we report a patient with oculodentodigital dysplasia (ODDD) caused by the c. 413G>A, p.Gly138Asp mutation in the gap junction protein alpha-1 gene. The patient suffered from characteristic dysmorphic features of ODDD. Ophthalmological investigation disclosed microcornea and a shallow anterior chamber, as expected. Surprisingly, the patient had a normal axial length and moderate myopia on both eyes. To the best of our knowledge, this is the first report on ODDD associated with relative anterior microphthalmos and myopia.

Insulin-mediated phosphorylation of the proline-rich Akt substrate PRAS40 is impaired in insulin target tissues of high-fat diet-fed rats.

Clinical insulin resistance is associated with decreased activation of phosphatidylinositol 3'-kinase (PI3K) and its downstream substrate protein kinase B (PKB)/Akt. However, its physiological protein substrates remain poorly characterized. In the present study, the effect of in vivo insulin action on phosphorylation of the PKB/Akt substrate 40 (PRAS40) was examined. In rat and mice, insulin stimulated PRAS40-Thr246 phosphorylation in skeletal and cardiac muscle, the liver, and adipose tissue in vivo. Physiological hyperinsulinemia increased PRAS40-Thr246 phosphorylation in human skeletal muscle biopsies. In cultured cell lines, insulin-mediated PRAS40 phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002. Immunohistochemical and immunofluorescence studies showed that phosphorylated PRAS40 is predominantly localized to the nucleus. Finally, in rats fed a high-fat diet (HFD), phosphorylation of PRAS40 was markedly reduced compared with low-fat diet-fed animals in all tissues examined. In conclusion, the current study identifies PRAS40 as a physiological target of in vivo insulin action. Phosphorylation of PRAS40 is increased by insulin in human, rat, and mouse insulin target tissues. In rats, this response is reduced under conditions of HFD-induced insulin resistance.

Transient visual loss triggered by scuba diving in a patient with a petrous epidermoid and combined thrombotic risk factors.

A 25-year-old woman who developed transient neurological abnormalities after scuba diving is reported. The subsequent day she experienced transient left-side monocular blindness. Arterial ocular occlusion in apparently healthy young women is unusual, and a search for the cause of this devastating vascular event is mandatory. Occlusion of the left branch retinal artery, total occlusion of the left internal carotid artery, and a petrous apex epidermoid were found, together with a shortened prothrombin time (INR: 0.73), a slightly elevated serum cholesterol level (6.1 mmol/l) and combined thrombophilia (elevated FVIIIC plus type 2 sticky platelet syndrome). This case underlines the complex mechanism of thromboembolic diseases, and the importance of the acquired trigger (in the present case scuba diving) in addition to the long-term anatomical and biochemical risk factors.

Fine structure of the area subpostrema in rat. Open gate for the medullary autonomic centers.

The area subpostrema (ASP) is a V-shaped area, ventral and ventrolateral to the area postrema. It constitutes the upper border zone of the commissural portion of the nucleus of the solitary tract. The ASP is considered as a morphological and functional key area for the medullary autonomic center. The capillaries here, in contrast to the capillaries of the area postrema are not fenestrated but establish a specific staining for acetylcholinaestherase (AChE). The ASP contains a high density of fibers and terminals of several neuropeptides which are known to affect on NTS activity. Receptors of different neuropeptids and cathecholamines and a dense network of GFAP positive glial processes are found also here. The neurons and the glial cells of the ASP are connected with the AP and a bidirectional connection exists between the ASP and NTS.

Pituitary atrial natriuretic peptide of paraventricular nucleus origin.

Atrial natriuretic peptide-synthesizing neurons in the hypothalamic paraventricular nucleus constitute the major sources of ANP in the three lobes of the pituitary gland. Complete transection of the pituitary stalk eliminated 93% of ANP from the intermediate lobe, 47 and 77% from the anterior and the posterior lobes, respectively. Meantime, increased levels of immunoreactive ANP were measured in the median eminence, due to the accumulation of the peptide in the transected axons centrally to the transected stalk and in the paraventricular nucleus. It is likely that ANP neurons in the paraventricular nucleus innervate the pituitary, but those in the periventricular (median) preoptic nucleus and the organum vasculosum laminae terminalis may not contribute to the ANP innervation of the pituitary gland.

Projections of VIP/PHI neurons of the interstitial nucleus of Cajal in the rat.

Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Cajal. Unilateral surgical cut through the medial forebrain bundle failed to influence VIP/PHI mRNA expression in the Cajal nucleus while brainstem hemisection or unilateral transection of the medial longitudinal fascicle reduced it markedly, ipsilateral to the knife cuts. Thus, in contrast to forebrain projecting VIP neurons in the rostral periaqueductal gray, VIP/PHI neurons in the Cajal nucleus project downwards, to the lower brainstem.